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Cell Mol Neurobiol. 2018 Aug;38(6):1153-1178. doi: 10.1007/s10571-018-0587-4. Epub 2018 Apr 26.

Parkinson Disease from Mendelian Forms to Genetic Susceptibility: New Molecular Insights into the Neurodegeneration Process.

Author information

1
Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran.
2
Department of Neurology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
3
Human Genetics & Genomic Medicine, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.
4
Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran. mjaf1d14@soton.ac.uk.
5
Human Genetics & Genomic Medicine, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK. mjaf1d14@soton.ac.uk.

Abstract

Parkinson disease (PD) is known as a common progressive neurodegenerative disease which is clinically diagnosed by the manifestation of numerous motor and nonmotor symptoms. PD is a genetically heterogeneous disorder with both familial and sporadic forms. To date, researches in the field of Parkinsonism have identified 23 genes or loci linked to rare monogenic familial forms of PD with Mendelian inheritance. Biochemical studies revealed that the products of these genes usually play key roles in the proper protein and mitochondrial quality control processes, as well as synaptic transmission and vesicular recycling pathways within neurons. Despite this, large number of patients affected with PD typically tends to show sporadic forms of disease with lack of a clear family history. Recent genome-wide association studies (GWAS) meta-analyses on the large sporadic PD case-control samples from European populations have identified over 12 genetic risk factors. However, the genetic etiology that underlies pathogenesis of PD is also discussed, since it remains unidentified in 40% of all PD-affected cases. Nowadays, with the emergence of new genetic techniques, international PD genomics consortiums and public online resources such as PDGene, there are many hopes that future large-scale genetics projects provide further insights into the genetic etiology of PD and improve diagnostic accuracy and therapeutic clinical trial designs.

KEYWORDS:

Autophagy; GWAS meta-analysis; Mitochondrial dysfunction; Neurodegeneration; Oxidative stress; Parkinson disease

PMID:
29700661
PMCID:
PMC6061130
DOI:
10.1007/s10571-018-0587-4
[Indexed for MEDLINE]
Free PMC Article

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