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1. |
role of alpha-Syn in the induction of p-GSK-3beta, and the importance of this kinase in the genesis and maintenance of neurodegenerative changes associated with Parkinson's disease. |
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2. |
the pivotal role of membrane attachment and transglutaminase-mediated intermolecular cross-linking for the propagative misfolding and aggregation of alpha-synuclein |
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3. |
Reported are binding constants and stoichiometry under near-physiological conditions for the binding of Cu(II) to wild-type alpha-synuclein and two separate single mutation proteins that are associated with familial Parkinson's diseases. |
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4. |
Studies of alpha-synuclein fibrillation show the utility of fluorine-labeled nuclear magnetic resonance; the data indicate that fibrillation is not accompanied by the formation of large quantities of low molecular weight intermediates. |
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5. |
the 3'UTR of human SNCA, as a whole, and rs17016074, in particular, are loci of potential clinical importance for Parkinson disease. |
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6. |
The presence of MSA-like alpha-synuclein oligodendrogliopathy and related to it pro-inflammatory microenvironment may compromise the connectivity and neurorestorative outcome of striatal grafts. |
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7. |
The ability of alpha-synuclein to inhibit proteasome activity in SH-SY5Y neuroblastoma cells is related to its propensity to assemble into filaments. |
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8. |
The data of this study suggested that dosage and sequence changes are a rare cause of parkinson disease, but variation in the promoter and 3' region of SNCA convey an increased risk for parkinson disease. |
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9. |
SNCA multiplications, through different degrees of alpha-synuclein overabundance in the central and peripheral nervous system, may generate different disease phenotypes with extrapyramidal parkinsonian symptoms. |
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10. |
This study findings suggest that SNCA REP1 genotype and alcohol use disorders are independently associated with Parkinson disease. |
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11. |
The results demonstrated that KTKEGV repeats may have a significant role in keeping native unfolded status of alpha-synuclein. |
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12. |
Results characterize alpha-synuclein conformational ensembles at neutral and low pH in order to understand how the altered charge distribution at low pH changes the structural properties of these ensembles and leads to an increase in aggregation rate. |
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13. |
cell-to-cell transmission of alpha-synuclein aggregates and provide critical insights into the mechanism of pathological progression in PD and other proteinopathies. |
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14. |
The presence of any form of alpha-synuclein polymer, from small oligomers to amyloid fibrils, is abnormal and may be problematic for the normal activities of cells, thereby resulting in neurodegeneration. |
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15. |
introduction of V40D and V74D mutations in A53T nearly ends its aggregation propensity, increases its solubility and positively enhances its thermodynamic stability. |
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16. |
Neuropathologic examination of 10 brains with clinico-pathologically verified postencephalitic parkinsonism confirmed widespread neurodegeneration while Lewy bodies and neurites or any other alpha-synuclein deposits were completely absent. |
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17. |
G2019S mutation in Lrrk2 may cause Parkinson disease by generating pathological levels of phosphorylated alpha synuclein. |
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18. |
Our data identify the ability of LRRK2 to form inclusion-like aggregates that do not associate with alpha-synuclein. |
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19. |
In this studt no SNCA mutations were identified. |
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20. |
Six self-aggregation-defective alpha-synuclein mutants completely inhibit the fibrillation of both wild-type and Parkinson's disease-linked alpha-synuclein variants. |
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21. |
In this study found that modest Modest associations (uncorrected P < 0.05) were observed for common variants around SNCA in Australia patient with Parkinson's disease. |
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22. |
These sex hormones, especially estriol, significantly exert anti-aggregation and fibril-destabilizing effects; and hence, could be valuable preventive and therapeutic agents for alpha-synucleinopathies. |
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23. |
study finds that the Parkinson's disease-linked alpha-Synuclein mutation E46K does not interfere with C-terminal-to-N-terminal contacts & instead enhances such contacts |
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24. |
The increased prevalence of alpha-synuclein and beta-amyloid in the brains of older HIV-infected individuals may predict an increased risk of developing neurodegenerative disease. |
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25. |
The content of mRNA for alpha-synuclein was elevated in the peripheral lymphocytes of patients with alcohol dependence syndrome. |
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26. |
mutations modifying copy number of alpha-synuclein gene do not significantly affect the pathogenesis of the autosomal dominant form of ParkinsonTs disease in patients from Russia. |
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27. |
activation of insulin-like growth factor 1 pathway can rescue alpha-synuclein toxicity and suppress alpha-synuclein aggregation through the activation of PI3K/Akt pathways. |
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28. |
The single nucleotide polymorphism at the SNCA locus were significantly associated with risk for increased risk for the development of multiple system atrophy (combined p = 5.5 x 10(12); odds ratio 6.2). |
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29. |
Elevated human alpha-synuclein alters presynaptic plasticity in the corticostriatal pathway, possibly reflecting a reduction in glutamate at corticostriatal synapses by modulation of adenylyl cyclase signaling pathways. |
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30. |
All four alpha-synuclein isoforms were affected in dementia with LB (Lewy bodies), most parkin transcript variants in common LB disease, and all synphilin-1 isoforms in Parkinson disease. |
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31. |
identified alpha-synuclein 98, which lacks exons 3 and 5. mRNA expression analyses in non-neuronal tissue revealed that alpha-synuclein 98 is a brain-specific splice variant with varying expression levels in different areas of fetal and adult brain. |
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32. |
oligomeric ASYN triggers the initial activation of the apoptotic pathway, which is however blocked downstream of the mitochondrial checkpoint, thus leading to a death combining in a unique fashion both apoptotic and non-apoptotic features |
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33. |
analysis of morphologically distinct oligomeric forms of alpha-synuclein |
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34. |
A30P alpha-synuclein has a negative impact on olfactory neurogenesis and suppression of A30P alpha-synuclein enhances survival of newly generated neurons in olfactory bulb. |
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35. |
Data show that alpha-synuclein pathology is less severe in the piriform cortex than in the primary olfactory cortex in the cases of Parkinson's disease and Lewy bodies. |
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36. |
The results indicate that endogenous GRK3 and GRK6, but not GRK2 or GRK5, contribute to Ser129 phosphorylation of alphaS in HEK293 cells. |
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37. |
synphilin-1A has a novel role as a regulator of SIAH activity, modulating alpha-synuclein, and formation of Lewy body-like inclusions |
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38. |
Sporadic PD cases showed a statistically significant decrease of the fold change (FC) of SNCA (FC = 0.31, P = 0.00001) gene expressions in the substantia nigra & amygdala (SNCA: FC = 0.49, P = 0.02) versus healthy controls. |
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39. |
The A30P missense mutation and multiplication mutations within SNCA are confirmed to be a rare cause of early-onset Parkinson disease. |
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40. |
The authors show here that substoichiometric concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) can inhibit the fibrillation of alpha-synuclein (alpha-Syn), due to non-covalent binding of DOPAC to alpha-Syn monomer. |
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41. |
Conversion of wild-type alpha-synuclein into mutant-type fibrils and its propagation in the presence of A30P mutant. |
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42. |
the simulations of the mutants suggest how changes in the structure and dynamics of alpha-synuclein may affect its biological role. |
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43. |
The lower alpha-syn levels in AD, as well as the association of alpha-syn reduction with AD severity, approximated by MMSE, suggests that it may be a general marker of synapse loss, a hypothesis that warrants further investigation. |
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44. |
CSF alpha-synuclein levels are not sensitive diagnostic markers to discriminate DLB from AD. However, the lower alpha-synuclein levels in DLB patients suggest a reduction in CSF alpha-synuclein and increased alpha-synucleinopathy in the brain. |
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45. |
Recombinant adeno-associated virus 2-mediated delivery of mutant (A53T) human alpha-synuclein into the substantia nigra results in protracted neurodegeneration with significant dopaminergic loss by 17 weeks. |
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46. |
The study demonstrated overexpression of mutated alpha-syn(A30P) exacerbates the aging process and leads to impaired synaptic plasticity. |
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47. |
alpha-synuclein is directly phosphorylated at Ser-129 by PLK2 |
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48. |
Phosphorylation does not play an active role in the accumulation of cytotoxic alpha-synuclein aggregates. |
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49. |
The results suggest that alpha-synuclein expression regulated by inflammatory signals may contribute to neurodegenerative processes in MS lesions. |
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50. |
LD between associated marker alles located across the SCNA gene suggests that a single genetic effect might explain the association in the promoter and 3' regions. |
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51. |
The APOE genotype (APOE epsilon2 or APOE epsilon4 alleles) and SNCA-REP1 polymorphism do not seem to influence olfaction in PD. |
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52. |
Proteasome function is not affected by UCH-L1(membrane associated form), suggesting that it may negatively regulate the lysosomal degradation of alpha-synuclein. |
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53. |
alpha-Syn accumulation causes complex cellular responses, which if persist may compromise cell viability. |
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54. |
Experiments using alpha-Syn deletion mutants indicated that interactions between the Hsp70 substrate binding domain and the alpha-Syn core hydrophobic region underlie assembly inhibition. |
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55. |
The molecular basis and clinical relevance of statistically decreased alphaSyn pathology in schizophrenic brain versus aged controls is unknown and needs further elucidation as will be necessary for its incidence and relevance in chronic affective diso... |
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56. |
Data show that aberrant aggregation and Lewy body-like inclusion formation of alpha-synuclein in cytoplasm of HEK293 cell induced by overexpression of wild-type can be blocked by RNAi. |
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57. |
Inhibition of alpha-synuclein fibril assembly by small molecules: analysis using epitope-specific antibodies is reported. |
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58. |
study evaluated changes in whole genome expression in dopaminergic neuroblastoma cells caused by RNA interference of SNCA; expression of 361 genes was altered at least+/-1.5-fold with 82 up-regulated and 279 down-regulated |
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59. |
Effect of alpha synuclein (alphaSyn) on phospholipase D (PLD) activity might be due to increased endoplasmic reticulum-related stress associated with alphaSyn overexpression but is not likely due to specific or direct interaction between alphaSyn and PLD. |
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60. |
The distribution of the alleles of the dinucleotide repeats variants of alpha-synuclein gene promoter region in Parkinson's disease cases was significantly different from that in the healthy controls. |
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61. |
This work quantitates the average nucleation and growth rate constants for alpha-synuclein aggregation and supports the hypothesis of the formation of a partially folded intermediate that promotes aggregation at higher temperatures or lower pH. |
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62. |
The phenotype associated with SNCA multiplications correlates with the number of copies of the gene and provides the first insight into the mechanisms underlying SNCA multiplication. |
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63. |
Data show that the pathological deposits with antibodies against synuclein alpha has involved in the neuropathogenesis of the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. |
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64. |
Results show that as well as having a number of effects on cellular events upstream of mitochondrial dysfunction, alpha-synuclein affects pathways downstream of superoxide production, possibly involving regulation of NOS activity. |
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65. |
non-phosphorylated alpha-synuclein carboxyl terminus pulled down protein complexes that were highly enriched for mitochondrial electron transport proteins, whereas alpha-synuclein carboxyl terminus phosphorylated on either Ser-129 or Tyr-125 did not |
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66. |
The proapoptotic effects of alpha-synuclein might be mediated at least in part by the impairment of NF-kappaB signaling pathway which involves GSK3beta. |
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67. |
These data suggest that up-regulated alpha-synuclein expression inhibits the activity of vesicular monoamine transporter-2. |
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68. |
These results demonstrate that 4-oxo-2-nonenal induced an almost complete conversion of monomeric alpha-synuclein into 40-80 nm wide and 6-8 nm high soluble beta-sheet-rich oligomers with a molecular weight of approximately 2000 kDa. |
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69. |
These data show that overexpression of alpha-SYN alone, in the absence of overt neurodegeneration, is sufficient to trigger neuroinflammation with both microglial activation and stimulation of adaptive immunity. |
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70. |
Our data confirm the fatty acid binding properties of alpha-syn, and to a lesser extent beta-syn, but suggest that gamma-syn does not share this same characteristic. |
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71. |
Alpha-Synuclein conformation affects its tyrosine-dependent oxidative aggregation |
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72. |
Data suggest that the long-range intramolecular interactions between the N- and C-termini of alpha-synuclein are likely to be crucial to the fibrillation process. |
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73. |
Data suggest that tTG binds equally effective to wild-type and disease mutant alpha-synuclein variants . |
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74. |
replacement of glutamate by alanine at position 83 (E83A) abolishes the ability of dopamine to inhibit SNCA fibrillization |
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75. |
can modulate the function of microglia and influence inflammatory changes such as those seen in neurodegenerative disorders. |
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76. |
Data show that cardiac sympathetic denervation in Parkinson's disease links to SNCA duplication |
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77. |
Parkinson patients have markedly reduced levels of alpha-synuclein in cerebellum;this reduction is general, rather then correlates to the investigated polymorphisms in SNCA. |
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78. |
Impairment of two lysosomal pathways, chaperone-mediated autophagy and macroautophagy, or of more general lysosomal function, may be an initiating factor in alpha-synuclein accumulation and sporadic Parkinson's disease pathogenesis. |
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79. |
Overexpression of alpha-synuclein is sufficient to cause olfactory deficits in mice similar to that observed in patients with Parkinson's disease. |
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80. |
Genotype-specific mean onset ages in Parkinson's disease displayed a trend of decreasing onset age with increasing allele size. Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. |
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81. |
study identified a new family with SNCA duplication who developed parkinsonism, visual hallucination, and cognitive fluctuation |
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82. |
The results indicate that the N-terminus of alphaS is essential for the PUFA-induced alphaS oligomerization. |
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83. |
These results suggest for the first time that variation of alpha-synuclein modulates neurofibrillary tau pathology and support the recent observations of an interaction of alpha-synuclein and tau in neurodegeneration. |
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84. |
Cu and Fe showed differential binding pattern toward alpha-synuclein as revealed by intrinsic tyrosine fluorescence, thioflavin-T fluorescence, 1-anilino-8-naphthalenesulfonate-binding studies, and scatchard plot analysis. |
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85. |
Baicalein-stabilized oligomers are beta-sheet-enriched according to CD and Fourier transform infrared spectroscopy analyses. From small-angle X-ray scattering and atomic force microscopy, the oligomers were characterized as compact globular species. |
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86. |
Plays an important role in the development of Parkinson's disease; insertion of a single point mutation is sufficient to generate age-related decline in specific motor performance in transgenic mice. |
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87. |
Endocytic pathway is involoved in alpha-synuclein-induced neurotoxicity in transgenic C. elegans. |
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88. |
Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator) |
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89. |
Hsp104 likely protects dopaminergic neurons by antagonizing toxic alpha-synuclein assemblies and might have therapeutic potential for PD and other neurodegenerative amyloidoses |
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90. |
Alpha-synuclein concentration is reduced in cerebrospinal fluid specimens from Parkinson disease, and possibly from subjects with dementia with Lewy bodies (DLB) when compared to neurological controls. |
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91. |
alpha-synuclein toxicity may be dependent on the phosphorylation at Ser(129) that induces the UPRs, possibly triggered by the disturbed endoplasmic reticulum-Golgi trafficking |
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92. |
ASYN and Lamp2a are developmentally regulated in parallel in cortical neuron cultures and in vivo in the central nervous system, and they physically interact |
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93. |
only aggregated forms of extracellular alpha-synuclein can be cleared by cell-mediated uptake and degradation, and this might represent a mechanism of preventing neurons from exposure to potentially toxic alpha-synuclein. |
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94. |
cathepsin D is the main lysosomal enzyme involved in alpha-synuclein degradation |
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95. |
Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. |
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96. |
CHIP preferentially recognizes and mediates degradation of toxic, oligomeric forms of alphaSyn |
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97. |
There is evidence that a-synuclein aggregation is an early pathogenic event in LB disorders. |
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98. |
human alphaSyn-overexpressing mice under Thy1 promoter (Thy1-alphaSyn) display alterations of colonic function |
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99. |
decreased expression of Nurr1, which has been found in Parkinson's disease patients with Nurr1 mutations, was shown to transcriptionally increase alpha-synuclein expression |
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100. |
alpha-synuclein aggregation and alpha-synuclein toxicity are enhanced by Siah-1 mediated ubiquination |
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101. |
data suggest the lack of involvement of the SNCA promoter in the pathogenesis of dementia in Parkinson disease. Further studies in other populations are needed to confirm these results |
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102. |
SNCA dosage is responsible for parkinsonism, autonomic dysfunction, and dementia observed within each family. Dysregulated expression of wild-type alpha-synuclein results in parkinsonism. |
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103. |
FGF20 is associated with Parkinson's disease synergistically with SNCA. |
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104. |
The numbers of neuronal and glial inclusions, and the extent of neuritic changes, correlated with the PD stage (P < 0.001). These findings suggest that intrinsic neostriatal neurons degenerate through alphaS aggregation during PD progression. |
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105. |
These findings have implications not only for normal alpha-Syn function in TH regulation, but also for measuring cell loss that is associated with synucleinopathy. |
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106. |
These results imply a direct role for alpha-synuclein in mitochondrial physiology, especially under pathological conditions, and in principle, link alpha-synuclein to other Parkinson's disease genes in regulating mitochondrial homeostasis. |
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107. |
phosphorylation at Ser-129 increases the conformational flexibility of alpha-syn and inhibits its fibrillogenesis in vitro but does not perturb its membrane-bound conformation |
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108. |
alpha-synuclein reacts with tyrosinase and may have a role in Parkinson disease |
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109. |
EPR spectroscopy, in conjunction with site-directed mutagenesis and isotopic labeling, was used to identify a minimum of four Cu2+ binding modes adopted by full length human alpha-synuclein between pH 5.0-7.4. |
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110. |
Solid-state NMR reveals structural differences between fibrils of wild-type and disease-related A53T mutant SNCA. |
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111. |
These results suggest that microglia may be the major scavenger cells for extracellular alpha-synuclein aggregates in brain parenchyma, and that clearance may be regulated by the activation state of these cells. |
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112. |
These findings suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by alpha-synuclein. |
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113. |
These results indicate a possible role for alpha-synuclein in anxiety-like behaviours. |
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114. |
These data provide novel explanations for the presence of hyperphosphorylated Ser129 alpha-syn in pathologic inclusions. |
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115. |
link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism |
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116. |
Data describe the characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR. |
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117. |
DJ-1 inactivation may promote alpha-syn aggregation and the related toxicity, and in this model HSP70 is involved in the antioxidant response and in the regulation of alpha-syn fibril formation |
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118. |
analysis of iron-induced pore-forming alpha-synuclein oligomers |
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119. |
These data collectively indicate that the dimeric species of wild type alpha-synuclein and its mutants can bind and cause membrane perturbations. |
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120. |
We conclude that other environmental agents could play a key role in inducing programmed cell death in cells of PD patients with mutant alpha-synuclein. |
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121. |
Results show that the channel activity, alpha-helical content, thermal stability of membrane-bound alpha-synuclein (alphaS) may have a role in the normal function and/or pathophysiology of the protein. |
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122. |
alpha-synuclein levels are influenced by genetic variability in the promoter and 3' region of the SNCA gene in vivo. |
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123. |
mitochondrial accumulated alpha-synuclein may interact with complex I and interfere with its functions. |
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124. |
accumulation of alpha-synuclein might contribute to the pathogenesis of PD and other Lewy body diseases by promoting alterations in parkin and tubulin solubility |
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125. |
Results provide a structural analysis of the conformational characteristics of the unstructured peptide, alpha-synuclein. |
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126. |
The aggregation behavior of alpha- and beta-synuclein as well as a series of chimeric variants were compared by exploring the structural transitions that occur in the presence of a widely used lipid mimetic, sodium dodecyl sulfate (SDS). |
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127. |
Pathologically confirmed Lewy body disease clinically characterized by progressive parkinsonism and cognitive dysfunction is caused by SNCA duplication |
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128. |
In this study 20-100% of alpha-synuclein-positive Lewy bodies in Parkinson disease patients contain LRRK2. |
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129. |
There is an increased risk of Parkinson disease with increasing synuclein-alpha (SNCA) dinucleotide repeat sequence variablility in a population exposed to pesticides. |
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130. |
Transgenic alpha-synuclein accumulation contributes to alterations in neurogenesis by reducing the survival of neural precursor cells in the hippocampus via downregulation of Notch-1 expression. |
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131. |
These findings demonstrate that alpha-synuclein acts as a potent inflammatory stimulator of microglial cells, and that inhibitors of such stimulation might be beneficial in the treatment of Parkinson's disease and other synucleinopathies. |
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132. |
review:Isoform Synphilin-1A inclusions recruit both alpha-synuclein and synphilin-1. Aggregation of synphilin-1 and synphilin-1A seems to be protective to cells |
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133. |
Truncated human alpha-synuclein is deleterious to the development and survival of nigral dopaminergic neurons in transgenic mice. |
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134. |
alpha-synuclein promoter polymorphism and smoking was associated with Parkinson's disease |
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135. |
Because stimulus-reward learning may be mediated by the basal ganglia and context learning may be related to the medial temporal lobe, our data raise the possibility that dopaminergic signals regulated by SNCA inversely affect these memory systems. |
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136. |
Structural properties and propensities to form fibrils of alpha-synuclein at the initial stage were investigated. |
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137. |
More than 99% of alpha-synuclein in human blood is present in the peripheral blood cells, with the remainder in plasma. |
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138. |
Alpha-Synucleinopathy is common in older people, and frequently associated with Alzheimer disease-type pathology. An unexpectedly high proportion with a cortical form of Lewy body disease was identified. |
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139. |
Identification of sequence determinants regulating fibrillation of amyloidogenic proteins may provide valuable information for designing peptide analog drugs to prevent protein amyloidosis. |
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140. |
monoubiquitylation by SIAH1 and SIAH2 represents a possible trigger event for alpha-synuclein aggregation and Lewy body formation |
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141. |
Data showed that that alphaB-crystallin interrupted alpha-synuclein aggregation at its earliest stages, most likely by binding to partially folded monomers and thereby preventing their aggregation into fibrillar structures. |
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142. |
the transcriptome and proteome of nitrated alpha-syn activated microglia, shown provide new potential insights into Parkinson disease mechanisms. |
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143. |
No mutations were found in SNCA in Parkinson disease patients from Portugal. |
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144. |
alpha-synuclein forms a high affinity lipid binding intermediate species during fibril formation. Oligomeric alpha-syn is known to be toxic & the high affinity binding species described here may correspond to a toxic species involved in Parkinson disease. |
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145. |
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator) |
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146. |
Observational study and meta-analysis of gene-disease association. (HuGE Navigator) |
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147. |
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) |
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148. |
Observational study of genotype prevalence. (HuGE Navigator) |
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149. |
Observational study of gene-disease association. (HuGE Navigator) |
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150. |
we develop a framework for thinking about alpha-synuclein in terms of initiating events and secondary processes that are required to trigger neuronal dysfunction and cell death--{REVIEW} |
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151. |
Further correlation studies are required in order to determine normal versus pathologic alpha-synuclein and how to detect such differences in clinical situations--{REVIEW} |
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152. |
Data suggest that genetic variability within the alpha-synuclein locus is associated with susceptibility to idiopathic Parkinson disease. |
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153. |
The accumulation of alpha-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids. |
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154. |
We present a case of a SNCA gene duplication patient with Parkinson disease and dementia. |
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155. |
Epitope mapping of an anti-alpha-synuclein monoclonal antibody has been performed. |
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156. |
alpha-syn causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive |
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157. |
alpha-Synuclein gene duplication is present in sporadic Parkinson disease |
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158. |
phosphorylation state of Ser-129 in human alpha-synuclein determines neurodegeneration in a rat model of Parkinson disease |
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159. |
analysis of 20 gene products that reproducibly enhanced misfolding of alpha-synuclein over the course of aging in human and C. elegans |
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160. |
oligodendroglial overexpression of alpha-synuclein may induce neuroinflammation related to nitrosive stress which is likely to contribute to neurodegeneration in multiple system atrophy |
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161. |
the assembly of mature alpha-synuclein fibrils is hierarchical: protofilaments --> protofibrils --> mature fibrils |
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162. |
Importance of deposition of alpha-synuclein as well as its phosphorylation in the pathogenesis of alpha-synucleinopathies. |
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163. |
Oligomers and protofibrils of alpha-synuclein are cytotoxic, and that Lewy bodiess may represent a cytoprotective mechanism in Parkinson disease. [REVIEW] |
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164. |
Primary non-fibrillar and fibrillar alpha-synuclein aggregations occur in neurons in multiple system atrophy.[REVIEW] |
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165. |
Alpha-synuclein affects the micellar properties of polyunsaturated fatty acids, allowing docosahexaenoic acid to be present in a soluble rather than micellar form. |
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166. |
The present data indicate that mutation in the alpha-synuclein gene may predispose the protein to dopamine-induced aggregation, thereby contributing to disease pathogenesis. |
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167. |
We report here a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene. Nucleus accumbens and limbic areas of the cerebral cortex showed vacuolation, with clustering of microvacuoles around Lewy neurites. |
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168. |
Cellular oligomerization of SNCA is determined by the interaction of oxidized catechols with a C-terminal sequence. |
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169. |
The present study did not find any SNCA multiplications in a series of 58 pathologically confirmed MSA cases excluding this event as a common cause of MSA. |
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170. |
Data show that cortex in Parkinsonism-dementia complex is distinguished from Alzheimer's disease and progressive supranuclear palsy by its accumulation of abnormal alpha-synuclein and suggest that PDC is a synucleinopathy as well as a tauopathy. |
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171. |
Our results indicate that Rep1 locus may be in linkage disequilibrium (LD) with a mutation in the gene or itself could be a risk factor for SPD. |
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172. |
alpha-Synuclein/dopamine transporter (DAT) protein complex formation accelerates DAT-mediated cellular dopamine (DA) uptake. |
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173. |
Casein kinase 2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies |
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174. |
Tau and alpha-synuclein are involved in shared or converging pathways in pathogenesis of Parkinson's disease(PD). Tau inversion influences development of cognitive impairment and dementia in patients with idiopathic PD. |
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175. |
These data strongly suggest that halpha-syn140m undergoes constitutive phosphorylation, and at least casein kinase-2 is involved in the phosphorylation. |
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176. |
A comparison of the structural and dynamic properties of the free states of all three synucleins, is reported in order to shed light on differences that may help to explain their different propensities to aggregate. |
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177. |
alpha-Syn phosphorylation caused by FeCl2 is due to casein kinase 2 upregulation |
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178. |
alpha-synuclein fibril structure analysis by site-directed spin labeling |
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179. |
Identificaton of a tilted peptide in alpha-synuclein, which could be involved in the toxicity induced during amyloidogenesis of alpha-synuclein. |
|
|
180. |
The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish Parkinson's disease patients. |
|
|
181. |
The plasma concentration displayed a median of 5.6 microg/L (range 2.1-19.4 microg/L) and there was no correlation with age and gender. Quantification of the plasma level of alpha-synuclein may be important as a biomarker for disease susceptibility. |
|
|
182. |
YPP1 suppresses lethality of A30P, but not of wild-type alpha-syn or the A53T mutant |
|
|
183. |
These results suggest that alpha-synuclein (1-120) renders dopaminergic cells more susceptible to stress, which may have important implications as to how this truncated protein might contribute to dopaminergic cell death in sporadic Parkinson's disease. |
|
|
184. |
mutant proteins form annular protofibrils(similar to pore-forming bacterial toxins), suggesting that inappropriate membrane permeabilization might be the cause of cell dysfunction and even cell death in amyloid diseases, as Alzheimers and Parkinsons |
|
|
185. |
conformation assumed upon binding to phospholipid membranes consists of two alpha-helical regions interrupted by a short break, which may be important for its pathogenic role |
|
|
186. |
Alpha-synuclein may play a role in phosphoinositol signaling that is coupled to the dopamine-G beta gamma-phospholipase C beta 2 pathway, ultimately leading to changes in calcium signaling. |
|
|
187. |
extracellularly secreted alpha-synuclein is processed via the activation of MMP-3 |
|
|
188. |
Our findings indicate that both parkin and alpha-SN share a common pathway in DA metabolism whose abnormality leads to accumulation of oxidative DA metabolites and subsequent cell death. |
|
|
189. |
Results show that Ser-129 of alpha-synuclein is selectively and extensively phosphorylated in synucleinopathy lesions, and that this phosphorylation promoted fibril formation in vitro. |
|
|
190. |
These results suggest that ubiquitination of alpha-synuclein is not required for inclusion formation and follows the fibrillization of alpha-synuclein. |
|
|
191. |
Ubiquitin, HSP27, parkin, and alpha-synuclein are cross-linked by gamma-glutamyl-epsilon-lysine bonds in Alzheimer's neurofibrillary tangles. Gln(99) is the site of the bond in synuclein. |
|
|
192. |
the reduced axonal transport exhibited by Parkinson's disease-associated alpha-synuclein mutants might contribute to perikaryal accumulation of alpha-synuclein and hence Lewy body formation and neuritic abnormalities in diseased brain |
|
|
193. |
suggest a novel physiological role for alpha-Syn in regulating SERT activity and may be of relevance in certain mental illnesses and in depression, in which SERT function is believed to be dysregulated. |
|
|
194. |
These data show that alpha-synuclein over-expressed in human neural embryonic cells results in patterns of degeneration that in some cases match features of Parkinson Disease. |
|
|
195. |
the NAC sequence is essential to beta-sheet formation and the aggregation originates from the beta-sheet intermediate, which may be implicated in the pathogenesis of Parkinson's disease |
|
|
196. |
Hyperosmotic stress induced phosphorylation of tyrosine 125 of alpha-synuclein via Pyk2/RAFTK; such phosphorylation was inhibited by related adhesion focal tyrosine kinase-associated protein |
|
|
197. |
Alpha-synuclein, but not its mutants (A53T, A30P), can protect CNS dopaminergic cells from the parkinsonism-inducing drug MPP+ but not from other neurotoxic agents tested |
|
|
198. |
A significantly elevated gene-specific alpha synuclein promoter DNA methylation pattern is observed in peripheral mononuclear cells of patients with chronic alcoholism. |
|
|
199. |
The selective susceptibility of nigral DA neurons is at least in part associated with factor(s) involved in handling of alpha-syn that is not shared by the VTA neurons. |
|
|
200. |
While the toxicity of alpha-synuclein is supported in this review article, an alternate interpretation for a neuroprotective role of alpha-synuclein in Parkinson's disease is also emerging. |
|
|
201. |
new mechanism of MPP+-induced dopaminergic toxicity by an interaction between mutant alpha-synucleins and the DAT, which is independent of the function of the proteasome. |
|
|
202. |
While tyrosinase overexpression induced apoptosis, co-expression of wild type or A53T mutant human alpha-Synuclein with tyrosinase further exacerbated cell death. |
|
|
203. |
Our results did not confirm the association reported previously and failed to identify a alpha-synuclein specific haplotype as susceptibility factor for essential tremor. |
|
|
204. |
directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with alpha-synuclein in Drosophila model of Parkinson's disease |
|
|
205. |
In a transgenic mouse model, ultrastructural analysis shows that human alpha-synuclein-enhanced green fluorescent protein overexpression results in the accumulation of electrodense inclusions and laminated bodies suggestive of lysosomal dysfunction. |
|
|
206. |
alpha-SYN aggregation in vitro was clearly accelerated by addition of FK506 binding proteins (E. coli SlyD FKBP & human FKBP12) & was counteracted by FK506, a specific inhibitor of FKBP. |
|
|
207. |
Frequency of spinal cord alpha-synuclein pathology in neurologically asymptomatic individuals older than 60 years of age. |
|
|
208. |
the effect of Ca(2+) on the acidic tail conformation in lipid-bound alpha-synuclein, lipid interaction occurs via the N-terminal domain,then a Ca(2+)-triggered membrane association of the acidic tail leads to alpha-synuclein aggregation. |
|
|
209. |
Gene dosage-dependent dysregulation of several genes important for dopaminergic phenotype in mice over-expressing wild-type human alpha-synuclein in substantia nigra at time points preceding neuronal cell death. |
|
|
210. |
The carboxy-terminus of alpha-syn may regulate aggregation of full-length alpha-syn and determine the diameter of alpha-syn filaments |
|
|
211. |
translocation into the nucleus and binding with histones represent potential mechanisms underlying alpha-synuclein pathophysiology |
|
|
212. |
Of medulloblastomas, 76% have immunoreactivity for either alpha- or beta-synuclein or both; no immunoreactivity for gamma-synuclein is seen in medulloblastomas. |
|
|
213. |
Neither the Ala53Thr nor the Ala30Pro mutation has a significant effect on the structure of folded alpha-synuclein. The Ala30Pro, but not the Ala53Thr, mutation appears to decrease the affinity of the protein for lipid surfaces. |
|
|
214. |
MPTP-inducible, strictly alpha-Syn-dependent, increased formation of Tau, suggesting convergent overlapping pathways in the genesis of clinically divergent diseases such as Alzheimer and Parkinson disease. |
|
|
215. |
alpha-synuclein has a highly dynamic structure, in agreement with the notion that alpha-synuclein is a natively unfolded protein. In contrast, fibrillar aggregates of alpha-synuclein exhibit a distinct domain organization. |
|
|
216. |
data suggest that accumulation of modified 22-24-kDa alpha-synuclein is a disease-specific event which may overwhelm the proteolytic system, leading to aberrant ubiquitination |
|
|
217. |
Altered alpha-synuclein homeostasis causing Parkinson's disease. |
|
|
218. |
The antiapoptotic property of Hualpha-Syn in neuronal cell lines is associated with the attenuation of caspase-3 activity without affecting the caspase-9 activity or the levels of cleaved, active caspase-3. |
|
|
219. |
interaction between endogenous DJ-1 and alpha-synuclein in normal and diseased brain tissue |
|
|
220. |
While over-expression of the mutant forms of alpha-synuclein enhances cell death in cells exposed to ischemia/reoxygenation or staurosporine, the wild type of alpha-synuclein protects against serum withdrawal-induced death and dopamine-induced toxicity. |
|
|
221. |
A normal function of alpha-synuclein is the negative modulation of human dopamine transporter (hDAT) activity. |
|
|
222. |
The axonal transport of tau occurs via a mechanism utilising fast transport motors, including the kinesin family of proteins, and that alpha-synuclein transport in neurons may involve both kinesin and dynein motor proteins. |
|
|
223. |
Variations in a complex repeat (NACP-Rep1) c. 10 kb upstream are associated with various levels of expression of the gene. |
|
|
224. |
wild-type alpha-synuclein is efficiently degraded in lysosomes by chaperone-mediated autophagy (CMA), but the pathogenic alpha- synuclein mutants are poorly degraded by CMA despite a high affinity for the CMA receptor |
|
|
225. |
phosphorylation of alpha-synuclein at S129 may be important for the formation of inclusions in PD and related alpha synucleinopathies |
|
|
226. |
analysis of ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants |
|
|
227. |
protofibril formation of alpha-synuclein is induced by dequalinium |
|
|
228. |
effects of pH and salt concentration on the in vitro assembly of human wild-type alpha-synuclein, particularly with regard to aggregation rate and aggregate morphology |
|
|
229. |
Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains |
|
|
230. |
The well ordered conformation of the helix-helix connector indicates a defined interaction with lipidic surfaces. |
|
|
231. |
Association of synuclein into higher molecular mass oligomers/protofibrils represents an alternate pathway from filament formation. |
|
|
232. |
Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred. |
|
|
233. |
Quantitative real-time PCR amplification of SNCA exons yielded results consistent with whole gene triplication in a Parkinson disease family |
|
|
234. |
perhaps p25alpha plays a pro-aggregatory role in the common neurodegenerative disorders hall-marked by alpha-synuclein aggregates |
|
|
235. |
Hsp70 chaperones inhibit reactive oxygen species generation and apoptosis by binding and sequestering alpha-syn |
|
|
236. |
Transgenic mice expressing human Ala53--> Thr Parkinson's disease mutant alpha-synuclein develop intraneuronal inclusions, mitochondrial DNA damage and degeneration, and apoptotic-like death of neocortical, brainstem, and motor neurons. |
|
|
237. |
No missense mutations or multiplications are found in the SNCA gene in patients with autosomal dominant Parkinson's disease. |
|
|
238. |
Authors' review shows that alpha-synuclein expression in the peripheral immune system might be one of the primary causes of immune abnormalities in patients with Parkinson's disease. |
|
|
239. |
Mice overexpressing alpha-synuclein, either the human wild-type or the Ala53Thr mutant form of the protein, displayed paraquat-induced protein aggregates but were completely protected against neurodegeneration |
|
|
240. |
gene multiplication appears not to be a major cause in the pathogenesis of sporadic Lewy body disease and young onset Parkinson disease in European population |
|
|
241. |
the important role of alpha-synuclein in neurotransmitter mobilization is not limited to dopaminergic terminals |
|
|
242. |
Ala-53-->Thr mutation causes neurodegenerative disease in transgenic mice |
|
|
243. |
alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells |
|
|
244. |
The fibrillation of alpha-synuclein at neutral pH was completely inhibited by methionine oxidation. |
|
|
245. |
Amino acid residues 64-100 of alpha-syn are the binding region responsible for its self-association. |
|
|
246. |
alpha-Synuclein binds saturably and with high affinity to characteristic intracellular structures that double-label for components of lipid rafts. The A30P mutation associated with Parkinson disease disrupts this interaction. |
|
|
247. |
Data suggest that post-translational modification of alpha-syn by nitration can promote the formation of intracytoplasmic inclusions that constitute the hallmark of Parkinson disease and other synucleinopathies. |
|
|
248. |
DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation |
|
|
249. |
truncated alpha-synuclein and proteasome have roles in alpha-synuclein aggregation |
|
|
250. |
The expression of the alphav integrin subunit in whole cell lysates was significantly downregulated in halpha-syn CG-4 oligodendrocyte progenitor cells. These results demonstrate a cytotoxic consequence of halpha-syn overexpression in CG-4 cells. |
|
|
251. |
The ability of alpha-synuclein to disrupt membranes correlated with the binding affinity of alpha-synuclein for the particular membrane lipid composition, and to the induced helical conformation of alpha-synuclein. |
|
|
252. |
Stabilization of the native, autoinhibitory structure of alphasynuclein constitutes a potential strategy for reducing or inhibiting oligomerization and aggregation in Parkinson's disease. |
|
|
253. |
NMR spectroscopy demonstrates that Parkinsonism-linked mutations greatly perturb specific tertiary interactions essential for the native state of alpha-synuclein. |
|
|
254. |
Binds with higher affinity to artificial membranes with the PS head group on the polyunsaturated fatty acyl chain rather than on the oleoyl side chain, indicating a stringent combinatorial code for the interaction of alpha-synuclein with membranes. |
|
|
255. |
DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibits A53T alpha-synuclein toxicity |
|
|
256. |
overexpression of wild-type or mutated human alpha-synuclein leads to dopamine neuronal cell death in rodents |
|
|
257. |
functions as a negative regulator of Ca(++)-dependent alpha-granule release from human platelets |
|
|
258. |
alpha-synuclein plays a role in neurotransmitter release and synaptic plasticity--REVIEW |
|
|
259. |
alpha-synuclein has a vital role in the modulation of dopamine transporter (DAT) function (review) |
|
|
260. |
Real-time monitoring of stimulated dopamine release in mice with different alpha-synuclein expression was used to study the role of alpha-synuclein in presynaptic dopamine recruitment. |
|
|
261. |
Data demonstrate that C-terminally truncated alpha-Synuclein (alpha-SynDeltaC) is normally generated from full-length alpha-Syn independent of alpha-Syn aggregation in brains and in cultured cells. |
|
|
262. |
results indicate a role of microtubules in the modulation of dopamine transporter (DAT) trafficking, and provide insight into a novel mechanism by which alpha-synuclein regulates DAT activity, by tethering the transporter to the microtubular network |
|
|
263. |
These results suggest that mutant alpha-synuclein leads to an impairment in vesicular dopamine storage and consequent accumulation of dopamine in the cytosol. |
|
|
264. |
Data show that both normal and mutant alpha-synuclein specifically interact with the mitochondrial complex IV enzyme, cytochrome C oxidase. |
|
|
265. |
The extent of formation of amyloid fibrils from alpha-synuclein is greatly enhanced by heparin and certain other glycosaminoglycans and charged polymers in vitro, observations that are relevant in the context of the etiology of Parkinson's disease. |
|
|
266. |
conformational behavior of human alpha-synuclein is modulated by familial Parkinson's disease point mutations A30P and A53T |
|
|
267. |
role of alpha-synuclein in the pathobiology of Parkinson's disease (review) |
|
|
268. |
alpha-SN may be one of the primary causes of the immune abnormalities observed in Parkinson's disease |
|
|
269. |
Combined analysis yielded a highly significant association between the 0 allele of the alpha-synuclein gene and a reduced risk for PD (OR=0.79, 95% CI 0.70-0.89, p=0.0001). |
|
|
270. |
Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins |
|
|
271. |
familial Parkinson's disease-linked A30P mutant alpha-Syn is defective in binding to phospholipid vesicles in vitro as determined by vesicle ultracentrifugation, circular dichroism spectroscopy, and low-angle X-ray diffraction |
|
|
272. |
we investigated the effects of inhibitors of the mitochondrial electron-transport chain on the aggregation of alpha-synuclein, a major protein component of Lewy bodies |
|
|
273. |
overexpression of CHIP inhibits alpha-synuclein inclusion formation and reduces alpha-synuclein protein levels |
|
|
274. |
located the primary binding for Cu(II) to a specific site in the N terminus, involving His-50 as the anchoring residue and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry |
|
|
275. |
SNCA triplication causes doubling of plasma alpha-synuclein & of its mRNA level in brain. At the protein level in brain, there is a greater effect on aggregated form deposition into insoluble fractions than on soluble alpha-synuclein expression. |
|
|
276. |
data indicated that there are two distinct families of structures: one consisting of relatively compact proteins with eight or less negative charges and one consisting of relatively extended structures with nine or more charges |
|
|
277. |
Proteins associated with impaired energy metabolism and mitochondria are particularly prone to oxidative stress associated with Ala30Pro-mutant alpha-synuclein in transgenic mice. |
|
|
278. |
These study demonstrate abnormal and distinct alpha-synuclein solubility and aggregation, and alpha-synuclein nitration without formation of Lewy bodies in the frontal cortex in PiD. |
|
|
279. |
These results suggest that the internalization of alpha-synuclein is temperature-insensitive and occurs very rapidly via a mechanism distinct from normal endocytosis. |
|
|
280. |
Results use data from multidimensional NMR spectroscopy to elucidate the molecular interactions between Abeta peptide and alpha-synuclein which may lead to onset of Lewy body dementia. |
|
|
281. |
We conclude that the alpha-synuclein (G209A) gene mutation genotype should be considered in the differential diagnosis of dementia with Lewy bodies, particularly in patients with European ancestry and a family history of Parkinson's disease. |
|
|
282. |
under physiological conditions, alphaSyn exists as diverse conformational isomers which exhibit distinct propensities for aggregation and fibril formation |
|
|
283. |
Dopamine modulates differently the stability of protofibrils and fibrils composed of wild type or variants of alpha-syn (A30P and A53T) as probed by high hydrostatic pressure (HHP). |
|
|
284. |
This study found significantly lower levels of scna mRNA then control. |
|
|
285. |
Expression of alpha-synuclein may reflect the intricate role of alpha-synuclein in the pathogenesis of parkinson disease. |
|
|
286. |
This newly identified poly-T polymorphism is a human-specific sequence; its length influences alpha-synuclein 126 expression levels; and, finally, it seems to exert a specific influence on normal aging. |
|
|
287. |
alpha-synuclein expression in human neurons is up-regulated during differentiation |
|
|
288. |
The alpha-synPD patients presented the illness at a younger age and also had lower prevalence of tremor when compared with the fPD patients. |
|
|
289. |
Results describe the structure of membrane-bound alpha-synuclein. |
|
|
290. |
its structural change including the post translational protein processing is a future interest in the molecular mechanism of multiple system atrophy |
|
|
291. |
In the present study we genotyped the NACP-REP1 polymorphism in 189 PD patients from southern Italy and 182 healthy control subjects. We failed to demonstrate an association of any NACP-REP1 allele with PD. |
|
|
292. |
A53T mutant human alpha-Syn exhibits increased stability in neuronal cell lines. |
|
|
293. |
total alpha-synuclein levels were just marginally elevated in dementia with Lewy bodies |
|
|
294. |
There was an increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes as compared with persons with neither. The combined effect of the two genotypes was the same as for either of the genotypes alone (separate and equal). |
|
|
295. |
decreased dopamine levels in substantia nigra neurons might promote alpha-syn aggregation in Parkinson's disease |
|
|
296. |
structural analysis of micelle-bound human alpha-synuclein and Parkinson disease variants |
|
|
297. |
Our data suggest a mechanism of 6-OHDA-induced dopaminergic toxicity involving an interaction of mutant alpha-synucleins with the DAT molecule and subsequent acceleration of cellular energy depletion that might be relevant for the pathogenesis of PD. |
|
|
298. |
Synphilin-1A may contribute to neuronal degeneration in alpha-synuclein mutations and provides insights into the role of inclusion bodies in neurodegenerative disorders. |
|
|
299. |
Results exclude high-affinity binding of FA molecules to specific alphaS sites and conclude alphaS bind to negatively charged membranes. |
|
|
300. |
The constant and abundant amyloid beta x-42 deposition in sporadic dementia with Lewy bodies suggests that alpha-synucleinopathy is also promoted by amyloid precursor protein dysfunction. |
|
|
301. |
The results indicate that chronic overexpression of human alpha-synuclein led to abnormal pharmacological responses in mice. |
|
|
302. |
A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss Parkinsonian brains. |
|
|
303. |
Given the concurrent loss of membrane binding by this alpha-synuclein mutation, we propose a membrane-bound functional complex with tau that might involve the actin cytoskeleton. |
|
|
304. |
In neural cells transfected with either normal or mutant A30P or A53T alpha-synuclein, downregulation of GTP cyclohydrolase, sepiapterin reductase, tyrosine hydroxylase and aromatic acid decarboxylase by wild-type but not mutant alpha-synuclein was noted |
|
|
305. |
Polymorphism of the alpha synuclein promoter region (non-amyloid component of plaques (NACP)-Rep1) is associated with an increased risk of Parkinson's disease (PD) in three separate studies. |
|
|
306. |
The critical rate-limiting step in nucleation of alpha-synuclein fibrils under physiological conditions is the oxidative formation and accumulation of a dimeric, dityrosine cross-linked prenucleus. |
|
|
307. |
The number of the N-terminal repeat domain in wild-type alpha-synuclein represents an evolutionary balance between the functional conformer of alpha-synuclein (alpha-helix and/or random coil) and its pathogenic beta-sheet conformation. |
|
|
308. |
results suggest that interactions between alpha-synuclein and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases |
|
|
309. |
The identification of pathogenic mutations in the three genes alpha-synuclein, parkin, and UCHL1 has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD). |
|
|
310. |
alphaS-PUFA interactions help regulate neuronal PUFA levels as well as the oligomerization state of alphaS, both normally and in human synucleinopathies |
|
|
311. |
Alpha-synuclein has a high affinity for packing defects in a bilayer membrane |
|
|
312. |
show using human cytochrome c plus H(2)O(2) as the source oxidative stress, that the tyrosines of alpha-synuclein are required for aggregation |
|
|
313. |
Although SNCA multiplication is a rare cause of Parkinson disease & Lewy body dementia, this study suggests other genetic variation in the SNCA gene, in trans-acting factors, & in post-transcriptional regulatory elements are likely to influence disease. |
|
|
314. |
The association of different NACP-Rep1 alleles with Parkinson's disease may be mediated, in part, by the effect of PARP-1, on SNCA expression. |
|
|
315. |
results suggest that nigral neuronal damage may release aggregated alpha-synuclein into substantia nigra, which activates microglia with production of proinflammatory mediators |
|
|
316. |
acceleration of fibrillization by molecular crowding |
|
|
317. |
Two mutations in the alpha-synuclein gene (A30P and A53T) promote the formation of alpha-synuclein protofibrils, suggesting a causal role for protofibril formation in Parkinson disease. |
|
|
318. |
Membrane-bound alpha-synuclein associates at the interfacial region of the lipid bilayer where it may favor a local concentration of certain phospholipids. |
|
|
319. |
Review highlights the debate about the precise mechanisms of alpha-synuclein toxicity to vulnerable neurons in the pathogenesis of Parkinson's disease. |
|
|
320. |
Intravesicular localization and secretion are part of normal life cycle of alpha-syn and might also contribute to pathological function of this protein in Parkinson disease. |
|
|
321. |
an engineered alpha-synuclein double mutant prevents wild type and familial Parkin variant fibril formation |
|
|
322. |
Overexpression of alpha-synuclein may play a role in cocaine-induced plasticity and regulation of dopamine synaptic tone. |
|
|
323. |
identified a number of independent copper binding sites in both the lipid-binding N-terminal domain and the highly acidic C-terminal domain |
|
|
324. |
Results suggest that DJ-1 may act as an oxidative-stress-induced chaperone to prevent alpha-synuclein fibrillation. |
|
|
325. |
Accumulation of alpha-synuclein (alpha-syn) in oligodendrocytes of transgenic mice overexpressing human alpha-syn promotes neurodegeneration and recapitulates several of the key functional and neuropathological features of multiple system atrophy |
|
|
326. |
Two families with SNCA duplication were identified among autosomal dominant hereditary Parkinson's disease patients. |
|
|
327. |
nitrative and/or oxidative stress results in distinct mechanisms of alpha-synuclein protein modifications that can influence the formation of stable alpha-synuclein fibrils |
|
|
328. |
consecutive cycles of compression-decompression under aggregating conditions lead to reversible dissociation of transthyretin and alpha-synuclein fibrils |
|
|
329. |
overexpression of human alpha-synuclein, particularly the mutant form, can cause human DA neuron death, suggesting that alpha-synuclein may have a primary role in the pathogenesis of PD. |
|
|
330. |
characterized the cytoplasmic alpha-synuclein aggregates using a fractionation procedure with which different aggregate species can be separated |
|
|
331. |
cysteine substitution at critical positions in the alpha-synuclein molecule can increase dimer formation and accelerate protein aggregation and cellular toxicity of alpha-synuclein |
|
|
332. |
Ubiquitination sites were found to be identical to those in filamentous alpha-synuclein. Parkinson disease-linked mutations. |
|
|
333. |
Role of the membrane on the aggregation process of alpha-synuclein. |
|
|
334. |
Alpha-synuclein has a role in altering proteasome function, protein synthesis, and stationary phase viability |
|
|
335. |
observation that amino acid residues 31-109 of constitute the core unit of the filaments |
|
|
336. |
alpha-synuclein filaments and oligomers have roles in proteasome inhibition |
|
|
337. |
Methionine oxidation plays an important role in inhibiting alpha-synuclein aggregation; the degree of inhibition of fibrillation by alpha-synuclein is proportional to the number of oxidized methionines. |
|
|
338. |
alpha-synuclein degradation and the pathogenesis of synucleinopathies are regulated by neurosin |
|
|
339. |
Data suggest that the ability of Hsp70 to prevent toxicity is distinct from degradation of alpha-synuclein and is dependent on its ATPase domain. |
|
|
340. |
A new protocol for preparing recombinant alpha-synuclein (AS) from E. coli has been developed with only two steps: (1) osmotic shock for release of AS-containing periplasm fraction and (2) ion-exchange chromatography for further purification of AS. |
|
|
341. |
Abeta enhances the development of cortical alpha-synuclein lesions in cases of Parkinson disease |
|
|
342. |
This study showing an influence of Rep1 polymorphism on age at onset of parkinson's disease. |
|
|
343. |
SUMO1 is involved in a modification of tau and alpha-synuclein that may also have implications for their pathogenic roles in neurodegenerative diseases |
|
|
344. |
Schizosaccharomyces pombe model that evaluates alpha-synuclein misfolding, aggregation & toxicity; results suggest that alpha-synuclein toxicity might be linked to its membrane binding capacity |
|
|
345. |
S. cerevisiae model to evaluate misfolding, aggregation & toxicity-inducing ability of wild-type alpha-synuclein & mutants; results suggest toxic species in yeast are smaller than the visible aggregates & toxicity may involve membrane association |
|
|
346. |
Preferential accumulation of normally produced Ser-129 phosphorylated alpha-synuclein is the key event responsible for the formation of Lewy bodies in various Lewy body diseases. |
|
|
347. |
alpha-synuclein levels are decreased in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease |
|
|
348. |
The binding of Hsp70 with PreAS only requires the substrate-binding subdomain, and the binding with AS nuclei requires the C-terminal lid subdomain as well. |
|
|
349. |
In a transgenic Drosophila model, aggregation of alpha-synuclein mediates toxicity to dopaminergic neurons in vivo. |
|
|
350. |
neurotoxicity is a mechanism for selective neurodegeneration in Parkinson disease. |
|
|
351. |
Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein |
|
|
352. |
Alpha-synuclein is up-regulated during apoptosis in neuroblastoma cells |
|
|
353. |
Pathological alpha-synuclein associated with inclusions in Parkinson disease is first evident as punctate perikaryal material that, via incorporation of p62 and ubiquitin, yields pale body-type structures from which Lewy body-type inclusions form. |
|
|
354. |
alpha-synuclein and alphaB-crystallin interact readily with each other and affect each other's properties, in particular alpha-synuclein fibril formation and alphaB-crystallin chaperone action |
|
|
355. |
an analysis of the intra-allelic variation at NACP-Rep1 in the alpha-synuclein gene |
|
|
356. |
parkin-mediated neuroprotection was associated with an increase in hyperphosphorylated alpha-synuclein inclusions, suggesting a key role for parkin in the genesis of Lewy bodies |
|
|
357. |
Abnormal alpha-synuclein aggregation in the amygdala is disease selective, but not restricted to disorders of alpha-synuclein and beta-amyloid. |
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358. |
Peripheral nerve studies show that alpha-synuclein (alpha-Syn) is almost exclusively transported in the slow component of axonal transport and that familial Parkinson's disease-linked alpha-Syn mutations have no obvious effects on its axonal transport. |
|
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359. |
Results suggest that the C-terminal domain acts as a regulator of alpha-synuclein aggregation. |
|
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360. |
the NACP-REP1 marker within the alpha synuclein gene may be associated with alcohol dependence |
|
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361. |
Results demonstrate that wild-type alpha-synuclein interacts with the pro-apoptotic molecules BAD and protein kinase C delta to protect dopaminergic neuronal cells against neurotoxic insults. |
|
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362. |
Our findings indicate that there is a high frequency of alpha-synucleinopathy in centenarians, SP-positive and AS-positive lesions may involve a synergistic interaction. |
|
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363. |
These findings suggest that the high membrane ion permeability caused by mutant alpha-synuclein may contribute to the degeneration of neurons in PD. |
|
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364. |
C-terminal of alpha-synuclein is an important regulator of aggregation in vivo and will help to understand the mechanisms underlying the pathogenesis of Lewy body disorders. |
|
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365. |
Targeting of alpha-synuclein to the nucleus promotes toxicity, but cytoplasmic sequestration is protective in cell culture & transgenic Drosophila; findings implicate nuclear alpha-synuclein in promoting nigrostriatal degeneration in Parkinson's disease |
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366. |
the age-related increases in nigral alpha-synuclein were non-aggregated and strongly associated with age-related decreases in tyrosine hydroxylase |
|
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367. |
Coexpression of the chaperone protein Hsp70, causes alpha-synuclein to adopt a different, open conformation, but Hsp70 does not alter alpha-synuclein-alpha-synuclein interactions. |
|
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368. |
alpha-synuclein strongly stimulates human astrocytes as well as human U-373 MG astrocytoma cells to up-regulate both interleukin IL-6 and ICAM-1; mutated forms are more potent stimulators than wild-type |
|
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369. |
Circular dichroism and nuclear magnetic resonance spectroscopy illustrate that the E46K mutation results in subtle changes in the conformation of the monomeric protein both free in solution and in the presence of SDS micelles. |
|
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370. |
the earliest defect following alphaSyn expression in yeast was a block in ER-to-Golgi vesicular trafficking; elevated expression of Rab1 protected against alpha-Synuclein-induced dopaminergic neuron loss in animal models of Parkinson Disease |
|
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371. |
mutated in parkinson disease, also a major component of Lewy bodies |
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372. |
The results show an absence of protective effects for the A30P/A53T mutants, and a differential cytoprotective role of alpha-synuclein against oxidants, which varies according to expression levels. |
|
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373. |
when expressed in yeast, it associated with the plasma membrane in a highly selective manner, before forming cytoplasmic inclusions; inhibited phospholipase D, induced lipid droplet accumulation, and affected vesicle trafficking |
|
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374. |
genome-wide screens were performed in yeast to identify genes that enhance the toxicity of alpha-synuclein; genes that modified alpha-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport |
|
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375. |
linkage to six chromosomal regions and have identified three causative genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1) in Parkinson disease |
|
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376. |
results provide indirect evidence on how beta-sheets assemble into alpha-synuclein fibrils on a nanometer scale |
|
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377. |
Cocaine abusers have an overexpression of alpha-synuclein in dopamine neurons. |
|
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378. |
Regulation of alpha-synuclein expression: implications for Parkinson's disease. Review. |
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379. |
role of aggresomes in cell viability was addressed in the context of over-expressing alpha-synuclein and its interacting partner synphilin-1 |
|
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380. |
subtle sequence changes in alpha-synuclein could significantly alter interaction with membrane bilayers |
|
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381. |
Heat shock protein 70 inhibits alpha-synuclein fibril formation |
|
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382. |
the alpha- and gamma-synucleins regulate proteasomal function and beta-synuclein acts as a negative regulator of alpha-synuclein |
|
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383. |
anionic surfaces presented as micelles or vesicles can serve to nucleate alpha-synuclein fibrillization |
|
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384. |
Loss of alpha-synuclein may contribute to frontal lobe dysfunction in aging and Alzheimer's disease, and may reflect subtle loss of presynaptic proteins in intact synapses. |
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385. |
functional effects of missense mutation on phospholipid binding and filament assembly of alpha-synuclein |
|
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386. |
Data show that double-stranded DNA, either linear or supercoiled, interacts with wild-type alpha-synuclein, leading to a significant stimulation of alpha-synuclein assembly into mature fibrils. |
|
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387. |
Alpha-Synuclein expression was observed in all fetal human organs examined. In adult human tissues the high expression of alpha-synuclein was maintained in the brain, whereas in other organs the expression was greatly reduced. |
|
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388. |
Overexpression of alpha-synuclein induced an early and progressive behavioral phenotype that can be detected in multiple tests of sensorimotor function. |
|
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389. |
Our data provide evidence that overexpression of mutated human A30P alpha-synuclein in mice leads to a reduced size of the dopamine storage pool. |
|
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390. |
Behavior analysis of transgenic mice expressing A53T mutant human alpha-synuclein shows a progressive reduction of spontaneous vertical motor activity in both mutant lines correlating with the dosage of overexpression. |
|
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391. |
Alpha-synuclein protects nerve terminals against injury and suggests that this activity operates in conjunction with CSPalpha and SNARE proteins on the presynaptic membrane interface. |
|
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392. |
The Human wild type (WT) and mutant alpha-synuclein (alpha-syn) genes were overexpressed using a Tet-on expression system in stably transfected dopaminergic MN9D cells. |
|
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393. |
alpha-synuclein interacts with vesicle membranes containing sphingomyelin and cholesterol; the protein is capable of annealing defects in curved vesicle membranes, which may prevent synaptic vesicles from premature fusion |
|
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394. |
The composite Guam parkinsonism-dementia complex neuropathology profile of tau, alpha-synuclein and 8, 12-iso-iPF(2alpha)-VI isoprostane reported here more closely resembles that seen in other tauopathies including frontotemporal dementias (FTDs). |
|
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395. |
the central hydrophobic region is critical for beta-sheet formation and the conformational alteration is the foundation of protein abnormal aggregation |
|
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396. |
findings indicate that increased expression of beta-synuclein protein results in a reduction of alpha-synuclein protein expression |
|
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397. |
Transgenic mice with the disease-associated A53T mutant alpha-syn show oligomeric alpha-syn in nondegenerating dopaminergic neurons that do contain insoluble alpha-syn. Intraneuronal dopamine levels modulate alpha-syn aggregation & inclusion formation. |
|
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398. |
overexpression of alpha-synuclein apparently recapitulates several important features of brains with PD and dementia with Lewy bodies |
|
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399. |
we focus on the role of the pre-synaptic protein alpha-synuclein in altering the proteasom based on the results emerging from experimental models showing a mechanistic chain of events between altered alpha-synuclein--REVIEW |
|
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400. |
Genetic variations of the alpha-synuclein gene affect the development of sporadic PD. |
|
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401. |
These studies suggest that the microtubule system is a potential target of alpha-syn, and impairment of this system might have impacts on neuronal structure and function. |
|
|
402. |
A primary physiological role of alpha-Syn may be to regulate the homeostasis of monoamines in synapses, through modulatory interactions of the protein with monoaminergic transporters. |
|
|
403. |
variation in SNCA contributes to alcohol craving |
|
|
404. |
report of the first Korean Parkinson disease family with the Ala53Thr mutation in the SNCA gene that occurred on different haplotype from the original one in Greek and Italian families |
|
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405. |
examined the biochemical characteristics of the additional, higher molecular mass species of phosphorylated alpha-synuclein-positive polypeptides that also are recovered in the Sarkosyl-insoluble fraction of synucleinopathy |
|
|
406. |
oxidative stress, stress-activated kinases, and factors involved in autophagy up-regulate alpha-synuclein content. |
|
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407. |
alpha-synuclein overexpression augmented TNF-alpha-induced apoptotic cell death in U373 cells by induction of caspase activation |
|
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408. |
Caenorhabditis elegans transgenic for human alpha-synuclein demonstrate neuronal and behavioral perturbations that are dependent upon expression in specific neuron subtypes |
|
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409. |
These findings provide a link between mutations or over-expression of alpha-synuclein and apoptosis of dopaminergic neurons by lowering the threshold of these cells to oxidative damage. |
|
|
410. |
Review focuses on the fibrillization potential of alpha-synuclein and on its link with defects in protein degradation. |
|
|
411. |
In cases of Lewy body disease (LBD), alpha-synuclein does not exhibit binding to rabphilin but rather to rab3a, suggesting possible impairment of neurotransmitter exocytosis in LBD. |
|
|
412. |
consistent with the hypothesis that mutant alpha-synuclein disrupts vesicular dopamine compartmentalization, this effect was diminished in cells expressing mutant alpha-synuclein |
|
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413. |
Mutant alpha-synuclein accumulation impairs short-term changes in synaptic strength when neurotransmitter availability is limited due to enhanced release probability or repetitive synaptic activity. |
|
|
414. |
proteasomal inhibition by aggregated alpha-synuclein could be mediated by interaction with S6'. |
|
|
415. |
alpha-synuclein E46K mutation increases amyloid fibril formation |
|
|
416. |
agrin has a role in binding alpha-synuclein and modulating alpha-synuclein fibrillation |
|
|
417. |
PD-related genetic modifications of human alpha-synuclein, parkin, and DJ-1 disrupt the mitochondrial function in C. elegans |
|
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418. |
A putative environmental pathogen capable of passing the gastric epithelial lining might induce alpha-synuclein misfolding and aggregation in specific cell types of the submucosal plexus and reach the brain via a consecutive series of projection neurons. |
|
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419. |
Heat shock proteins may inhibit alpha-synuclein expression, accelerate alpha-synuclein degradation, thereby reducing the amount of alpha-synuclein protein and accordingly preventing its aggregation. |
|
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420. |
it is reported for the first time that transduced Tat-alpha-synuclein fusion protein protected against oxidative stress induced neuronal cell death by induction of HSP70 in vitro and in vivo |
|
|
421. |
These results suggest that in cells, alpha-syn is engaged in a fundamentally different mode of membrane interaction than the charge-dependent artificial membrane binding. |
|
|
422. |
These results indicate that the C-terminal portion of the membrane-bound alpha-syn is quite rigid and structured, at variance from current models of the membrane-bound protein. |
|
|
423. |
The present investigation uncovers the detailed binding propensities between metals and alpha-synuclein and has biological implications in PD. |
|
|
424. |
study shows aggregated oligomeric alpha-synuclein is internalized by dopaminergic cells & causes detrimental morphological changes prior to cell death; one mechanism by which it mediates cell death is disruption of tubulin polymerization into microtubules |
|
|
425. |
Casein kinase II (CKII) phosphorylates synphilin-1; beta subunit of this enzyme complex binds to synphilin-1. CKII-mediated phosphorylation of synphilin-1, rather than alpha-synuclein, modulates the aggregation into inclusion bodies. |
|
|
426. |
role of aggregation by tissue transglutaminase in Lewy body formation in Parkinson's disease and dementia with Lewy bodies |
|
|
427. |
role in pathogenesis of Parkinson disease |
|
|
428. |
Alpha-synuclein protofibril is stabilized by a dopamine-alpha-synuclein adduct. |
|
|
429. |
Protofibrillar alpha-synuclein, in contrast to the monomeric and fibrillar forms, binds synthetic vesicles very tightly via a beta-sheet-rich structure, causing transient and potentially cytotoxic permeabilization. |