• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Neuromuscul Disord. Author manuscript; available in PMC Dec 1, 2007.
Published in final edited form as:
PMCID: PMC1976411
NIHMSID: NIHMS15495

AβPP overexpression and proteasome inhibition increase αB-crystallin in cultured human muscle: relevance to inclusion-body myositis.

Abstract

Amyloid-β precursor protein (AβPP) and its fragment amyloid-β (Aβ) are increased in s-IBM muscle fibers and appear to play an important role in the pathogenic cascade. αB-crystallin (αBC) was shown immunohistochemically to be accumulated in s-IBM muscle fibers, but the stressor(s) influencing αBC accumulation was not identified. We now demonstrate, using our experimental IBM model based on genetic overexpression of AβPP into normal culture human muscle fibers, that: 1) AβPP overexpression increased αBC 3.7-fold (p= 0.025); 2) additional inhibition of proteasome with epoxomicin increased αBC 7-fold (p=0.002); and 3) αBC physically associated with AβPP and Aβ oligomers. We also show that in biopsied s-IBM muscle fibers, αBC was similarly increased 3-fold (p=0.025) and physically associated with AβPP and Aβ oligomers. We propose that increased AβPP is a stressor increasing αBC expression in s-IBM muscle fibers. Determining the consequences of αBC association with Aβ oligomers could have clinical therapeutic relevance.

Keywords: inclusion-body myositis, αB-crystallin, amyloid-β: amyloid-β precursor protein, cultured human muscle fibers

Introduction

s-IBM, the most common muscle disease of patients age 50 and older, is of unknown etiology and pathogenesis, and it lacks definitive treatment [reviewed in 1]. Light-microscopic features of s-IBM muscle biopsies include vacuolated muscle fibers, accumulation of intra-muscle-fiber multiprotein aggregates, and various degrees of lymphocytic inflammation [2]. Two hypotheses regarding the key pathogenic mechanisms involved in s-IBM are: a) an amyloid-β-related myodegenerative process, and b) an immune dysregulation [reviewed in 2,3]. Intriguingly, the s-IBM muscle-fiber phenotype has similarity to the Alzheimer-disease brain, such as accumulations of multiproteinaggregates containing proteins in congophilic alternate conformation, including amyloid-β (Aβ) [2].Reduction of 26S proteasome activity and features of aggresomes were recently demonstrated within s-IBM muscle fibers, and these were modeled in cultured human muscle by experimental overexpression of AβPP [4]. Abnormal increase of AβPP/Aβ appears to be an early upstream step in the IBM pathogenesis because a) AβPP/Aβ accumulation appears to precede other detected abnormalities ins-IBM muscle fibers [2], and b) several aspects of the IBM phenotype were produced in cultured normal human muscle fibers (CHMFs) after experimental long-term overexpression of AβPP [5-7]. Long overexpression of AβPP in muscle of transgenic mice also induced some aspects of the IBM phenotype [8-10]. Moreover, increased oligomerization of Aβ was associated with increased degeneration of CHMFs [11]. In other cells, Aβ oligomers are highly toxic, producing more cellular damage than fully fibrillar Aβ [12-16]. We have postulated that in s-IBM muscle fibers, Aβ toxicity may not be related to Aβ in the insoluble aggregates, but rather to a toxicity of its soluble oligomers and protofibrils [2].

αBC, a stress-responsive small heat-shock protein (sHSP), was shown immunohistochemically to be abnormally accumulated in muscle fibers of s-IBM and other myopathies [17]. Of particular interest was the report that in s-IBM, but not in other myopathies, αBC was accumulated not only in the structurally abnormal (vacuolated or otherwise obviously damaged) muscle fibers, but also in many fibers, termed “X-fibers”, which did not display “significant” morphologic abnormality [17], at that or an adjacent level of the muscle fiber (but did have internal nuclei or subtle tinctorial changes in modified trichrome staining in the published photos). It was proposed that increased αBC expression precedes other abnormalities in s-IBM muscle fibers [17]. The stressor(s) inducing αBC in s-IBM fibers was not identified, but it was suggested that αBC might be accumulated due to yet unidentified virus, and as such might play a protective role [17], or it might, either by itself or bound to another protein, induce an inflammatory response [17,18].

Since increased expression of αBC can occur under various stressful conditions [reviewed in 19,20], we hypothesize that in morphologically “undamaged” s-IBM muscle fibers, αBC is induced as a secondary reaction in response to the early increase in them of “morphologically invisible” soluble Aβ-oligomers (not in aggregates). To test this hypothesis, we studied αBC in cultured human muscle fibers shortly after AβPP-overexpression in them, before typical structural abnormalities developed. We also evaluated, both in CHMFs and in s-IBM muscle fibers, whether αBC physically associates with AβPP and Aβ oligomers. In this manuscript, we demonstrate the following: 1. By immunoblots, αBC is increased in a) CHMFs due to AβPP-overexpression and proteasome inhibition, and b) biopsied s-IBM muscle fibers. 2. In both, the CHMFs and s-IBM muscle fibers, αBC physically associates with AβPP and Aβ oligomers.

Material and Methods

Cultured human muscle fibers (CHMFs)

Cultures were established from satellite cells of archived portions of diagnostic muscle biopsies from patients who, after all tests were performed, were considered free of muscle disease [21].

In six culture sets, each established from a different biopsy, a 3 Kb 751 AβPP-cDNA, in either sense or anti-sense orientation, was transferred into three-week-old cultured muscle fibers, using a replication-deficient adenovirus (RDAV) vector, at 0.3×108 pfu/ml culture medium, as detailed [4-7]. (In this culture model, an increase of AβPP and Aβ is visible by immunoblots and Elisa within 24-48 hours after AβPP gene-transfer, and morphologic aspects of IBM appear approximately 14-21 days after the transfer.) Three days after transfer, experimental and control (non-AβPP-overexpressing) cultures were treated with 1μM epoxomicin (Biomol Research Laboratories, Plymouth Meeting, PA), an irreversible proteasome inhibitor [22]. 24 hours thereafter, the cultures were processed for light-microscopic immunocytochemistry, immunoblotting, and combined immunoprecipitation/immunoblotting, as described [4-7,11,23,24].

Light-microscopic immunocytochemistry

This utilized two antibodies against αBC: mouse monoclonal clone 1b6.1-3G4 (Stressgen Bioreagents, Victoria, BC), diluted 1:250 [17]; or a rabbit polyclonal antibody (Stressgen), diluted 1:250. Rabbit polyclonal antibody against γ-tubulin (Santa Cruz, CA), diluted 1:150, was used to identify aggresomes [4].

Immunoblots

These were performed as described [5,7,11,23,24]. In brief, 10μg of protein were loaded onto 12% NuPAGE gels (Invitrogen, Grand Island, NY), electrophoresed in MES-SDS NuPAGE buffer, transferred to nitrocellulose membranes, and immuno-probed with mouse monoclonal antibodies against αBC, diluted 1:1000. The blots were developed using the enhanced chemiluminescence system. Protein loading was evaluated by GAPDH and actin bands, visualized with a goat polyclonal anti-GAPDH antibody (1:400), and a mouse monoclonal anti-actin antibody (1:2000) (both from Santa Cruz, CA). Quantification of immunoreactivity was performed in 6 culture sets by densitometric analysis using the Kodak Gel Logic 440 imaging system (Eastman Kodak Company, Rochester, NY).

Combined Immunoprecipitation-Immunoblotting

To evaluate whether, in AβPP-overexpressing (“AβPP+”) CHMFs, αBC physically associates with AβPP and Aβ oligomers, we performed a 2-stage-combined immunoprecipitation-immunoblot technique, as described [23,24]. In brief, 100 μg of total muscle protein was immunoprecipitated in precipitation-buffer containing either 5 μg of 6E10 antibody against AβPP/Aβ (Signet, Dedham, MA), or 5 μg of antibody against αBC. The reaction mixture was incubated overnight at 4°C on an orbital shaker. The immunoprecipitated complex, containing IgG antibody, along with its bound target antigen and all proteins bound to that antigen, was pulled down using Protein G Sepharose 4 Fast Flow (Amersham Biosciences Corp. Piscataway, NJ) and incubating for 4 hours at 4°C. That solution was centrifuged for 5 minutes (16,000xg at 4°C) and supernatant removed. The precipitated sepharose immunocomplexes were three times washed with the precipitation buffer by centrifuging 5 minutes (16,000xg at 4°C). To break all bonds between antibody and target-antigen, and between target-antigen and its in vivo binding partners, the pellet was resuspended in 48 μl of 4X NuPAGE LDS sample buffer and 12 μl of 10X sample reducing agent (both Invitrogen, Carlsbad, CA), boiled for 10 minutes and then centrifuged for 5 minutes (16,000xg at 4°C). 10 μl of the supernatant was loaded onto 12% NuPAGE gels (Invitrogen, Grand Island, NY), electrophoresed in MES-SDS NuPAGE buffer, and transferred to nitrocellulose membranes. The electrophoresed protein products of the αBC-immunoprecipitate were immunoprobed with 6E10 anti-AβPP/Aβ antibody, and the products of the AβPP/Aβ immunoprecipitate was immunoprobed with anti-αBC antibody, each followed by an appropriate secondary antibody. To confirm specificity of the immunoprecipitation reaction, primary antibodies were omitted from the immunoprobing.

Biopsied muscle fibers

To evaluate whether αBC binds to AβPP/Aβ in s-IBM muscle biopsies, we performed αBC immunoblots and combined-immunoprecipitation-immunoblots of fresh-frozen diagnostic muscle biopsies obtained with informed consent. Five biopsies were s-IBM and 4 were normal with all our diagnostic studies. All diagnoses were based on our routinely-performed extensive clinical and laboratory studies [1].

Immunoblots

Immunoblots were performed as described above for CHMFs and recently detailed [4, 23-25].

Combined immunoprecipitation-immunoblot procedure

To evaluate if in s-IBM muscle fibers αBC physically associates with AβPP and/or Aβ, a combined immunoprecipitation-immunoblot technique was performed, essentially as above and as described [4, 23-25]. In brief, 100 μg of total muscle protein from s-IBM and control muscle biopsies were individually immunoprecipitated in precipitation buffer containing 5 μg of anti-αBC antibody, The immunoprecipitates were electrophoresed: a) on 12% NuPAGE gel in MES-SDS NuPAGE buffer to visualize Aβ oligomers, and b) on 4-12% NuPAGE gel in MOPS-SDS NuPAGE buffer to visualize AβPP. All other steps were as described above for CHMFs.

Statistical Analysis

These analyses were performed in all experiments using Student t-test. Significance level was set at p< 0.05. Data are reported as means ± SEM for all groups.

Results

Cultured human muscle fibers

Light-Microscopic Immunocytochemistry

In the cytoplasm of AβPP+ CHMFs, αBC was diffusely and more strongly immunoreactive than in control CHMFs (Fig.1 A,B). In about 80-90% of AβPP+ CHMFs, epoxomicin treatment induced large strongly-immunoreactive αBC aggregates, which colocalized with γ-tubulin, indicating that they were aggresomes [4] (Fig.1 C,D).

Fig.1
Single (A,B) and double (C,D) immunofluorescence of cultured human muscle fibers (CHMFs). A-C-α-BC; D-γ-tubulin. In AβPP-overexpressing CHMFs (B) αBC is strongly immunoreactive in contrast to control CHMFs (A), which have ...

Immunoblots

In all culture sets, αBC migrated as a 22 kDa band (Fig. 2A). Compared to untreated control cultures, αBC was increased: a) 3.7-fold (p= 0.025) in AβPP+ CHMFs; b) 3.4-fold (p=0.001) in epoxomicin-treated control CHMFs; and c) 7-fold (p=0.002) in epoxomicin-treated AβPP+ CHMFs (Fig.2 A, B). CHMFs overexpressing antisense AβPP did not have increased αBC (Fig. 2 C,D).

Fig.2
Cultured human muscle fibers. A-immunoblot of CHMFs lysates, using an antibody against αBC, illustrates increased αBC in epoxomicin-treated, in AβPP-overexpressing (AβPP+), and in combined AβPP+ and epoxomicin-treated ...

Combined immunoprecipitation-immunoblotting

Immunoprecipitation of proteins from AβPP+ CHMFs with 6E10 antibody, which recognizes both free Aβ and AβPP, followed by immunoprobing with an antibody against αBC, revealed a very strong αBC band of 22 kDa (Fig. 2E). Conversely, immunoprecipitation with an antibody against αBC, followed by immunoprobing with 6E10 antibody, revealed a strong band at 130 kDa corresponding to AβPP, and bands at 8,12 and 16 kDa corresponding to Aβ oligomers (dimers, trimers, and tetramers) (Fig.2 F,Fa). Those results indicate that αBC physically associates with AβPP and free Aβ oligomers. A 4kDa Aβ monomer was not identified. (The 26 and 50kDa bands of IgG resulting from the immunoprecipitation reactions are non-specific bystanders.)

Biopsied muscle fibers

Immunoblots

As in CHMFs, αBC migrated as a 22kDa band both in control and s-IBM muscle biopsies. As compared to controls, in s-IBM muscle fibers, αBC was increased 3-fold (p=0.025) (Fig.2 G,H).

Combined immunoprecipitation-immunoblotting

Immunoprecipitation of s-IBM muscle fibers with an antibody against αBC, followed by immunoprobing with 6E10 antibody, revealed a strong band at 130 kDa corresponding to AβPP (Fig.2 Ia) and two bands at 8 and 16 kDa corresponding to Aβ dimers and tetramers (Fig.2 Ib). Aβ monomer and trimer bands were not visible under these conditions. Control muscle fibers were negative. Those results indicate that in s-IBM muscle, similarly to CHMFs, αBC physically associates with AβPP and Aβ oligomers.

Discussion

As an sHSP, αBC is known to play a role in the cellular defense against improperly degraded, accumulated and toxic proteins [19,20]. αBC specifically recognizes and stabilizes proteins that have a propensity to aggregate and precipitate [19,20]. In Alzheimer brain, αBC binds to AβPP [26], and αBC mRNA is increased (referenced in [26]). In vitro, αBC prevents Aβ fibril growth and spontaneous fibril formation, binds Aβ, and prevents its aggregation [27-29]. However, when applied extracellularly to cultured rat neurons, concomitantly with Aβ, αBC increases Aβ cytotoxicity [28], possibly due to αBC’s influence in maintaining Aβ in its soluble oligomeric, highly cytotoxic form [28]. Several studies have demonstrated that Aβ and other amyloidogenic proteins exert their cytotoxicity when in the form of oligomeric intermediates or “pre-amyloid” protofibrils, and not while in the form of insoluble amyloid fibrils or aggregates [12-16].

In Alzheimer disease, Aβ oligomers are now considered more harmful that organized amyloid plaques [12-16]. Our studies of cultured human muscle fibers bearing the transthyretin Val122Ile mutation and overexpressing AβPP indicated that increased muscle fiber degeneration is associated with increased Aβ oligomerization [11]. Of interest is a recent study related to cultured cardiomyocytes which experimentally expressed both αBC bearing the R120G mutation, causing desmin-related myopathy [30], and a toxic amyloidogenic peptide PQ81 [31]. Those cardiomyocytes had pronounced aggresome formation but, interestingly, inhibition of the aggresome formation through additional expression of the wild αBC led to increased accumulation of PQ81 amyloidoligomers and increased cellular toxicity [31]. That study suggests that, while a mutated αBC causes aggregation of a toxic amyloidogenic protein, prevention of aggresome formation by maintaining amyloidogenic protein in the form of oligomers was associated with increased toxicity [31].

Our current study provides a novel demonstration that in human muscle fibers αBC is increased due to: a) AβPP overexpression (AβPP+), b) proteasome inhibition, and c) a combination of both has an additive effect. Moreover, αBC physically associates with AβPP and Aβ oligomers in human muscle fibers, both in AβPP+ cultures and in s-IBM muscle fibers. Our immunoblot studies also confirmed what was previously reported by immunohistochemistry [17], that αBC is significantly increased in s-IBM muscle fibers. In our culture IBM model, we studied αBC shortly after AβPP overexpression and before morphologic abnormalities were evident. We raise the possibility that the binding of αBC to Aβ oligomers might retard and diminish their fibrillization and aggregation into visible aggregates, thereby prolonging their existence as toxic oligomers (if αBC binding per se does not detoxify the oligomers). Those cultured muscle fibers mimic the normally-appearing IBM biopsied muscle fibers that have αBC increase without “significant” morphologic abnormalities [17]. Proteasome inhibition, which appears to be an important part of the s-IBM pathogenesis and in AβPP+ CHMFs, results in aggresome formation [4], additionally increased αBC expression and, in AβPP+ CHMFs, caused αBC accumulation in aggresomes, as previously shown in human glioma cells [32]. (In our studies, increased αBC in AβPP+ CHMFs is not due to the adenovirus transfer vector because using the same vector to transfer antisense AβPP cDNA did not result in increased αBC).

In summary, this experimental study 1) identified AβPP and/or oligomeric Aβ, its toxic proteolytic product, as probable stressors causing increased αBC in s-IBM muscle fibers that morphologically appear without significant damage, and 2) again supports an important upstream role of AβPP/Aβ in the s-IBM pathogenesis. Moreover, proteasome inhibition, which is present in s-IBM muscle fibers and is experimentally produced by AβPP overexpression in CHMFs [4], might additionally contribute to the αBC increase in s-IBM. Based on our data, and evidence of others in neuronal tissue [28], we propose that in s-IBM fibers αBC binding to Aβ oligomers with the “intent” to chaperone actually may be detrimental by preventing Aβ oligomers from assembling into the putatively non-toxic aggregates. Another possibly detrimental effect is that αBC bound to AβPP/Aβ might help induce or maintain the inflammatory reaction in s-IBM muscle [18]. Those putatively adverse reactions, if confirmed, could provide novel therapeutic targets. Alternatively, a beneficial αBC chaperoning effect in s-IBM muscle fibers can also be considered if the αBC binding is to a cytotoxic moiety of AβPP/Aβ. Our studies do not negate the possibility, as was previously suggested [17], that in s-IBM muscle fibers αBC might also be induced by other stressors, for example a yet unidentified virus, which has been proposed to play a role in the s-IBM pathogenesis [reviewed in 1-3] and which could be antecedent to the increased expression of AβPP/Aβ.

Acknowledgments

Acknowledgements. Supported by grants (to VA) from the National Institutes of Health (AG16768 Merit Award), the Muscular Dystrophy Association and The Myositis Association, and the Helen Lewis Research Fund. SW is on leave from the Department of Anatomy and Neurobiology, Medical University of Gdansk, Gdansk, Poland. OP is on leave from Department of Pathology and Animal Health, University of Naples Federico II, Naples, Italy.

References

1. Engel WK, Askanas V. Inclusion-body myositis: clinical, diagnostic, and pathologic aspects. Neurology. 2006;66:S20–29. [PubMed]
2. Askanas V, Engel WK. Inclusion-body myositis. A myodegenerative conformational disorder associated with Aß, protein misfolding, and proteasome inhibition. Neurology. 2006;66:S39–S48. [PubMed]
3. Dalakas MC. Inflammatory, immune, and viral aspects of inclusion-body myositis. Neurology. 2006;66:S33–38. [PubMed]
4. Fratta P, Engel WK, McFerrin J, Davies KJ, Lin SW, Askanas V. Proteasome inhibition and aggresome formation in sporadic inclusion-body myositis and in amyloid-beta precursor protein-overexpressing cultured human muscle fibers. Am J Pathol. 2005;167:517–526. [PMC free article] [PubMed]
5. Askanas V, McFerrin J, Baque S, Alvarez RB, Sarkozi E, Engel WK. Transfer of beta-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultured normal human muscle. Proc Natl Acad Sci U S A. 1996;93:1314–1319. [PMC free article] [PubMed]
6. Askanas V, McFerrin J, Alvarez RB, Baque S, Engel WK. βAPP gene transfer into cultured human muscle induces inclusion-body myositis aspects. Neuroreport. 1997;8:2155–2158. [PubMed]
7. McFerrin J, Engel WK, Askanas V. Impaired innervation of cultured human muscle overexpressing βAPP experimentally and genetically: Relevance to inclusion-body myopathies. Neuroreport. 1998;9:201–205. [PubMed]
8. Jin LW, Hearn MG, Ogburn CE, et al. Transgenic mice over-expressing the C-99 fragment of AβPP with an alpha-secretase site mutation develop a myopathy similar to human inclusion body myositis. Am J Pathol. 1998;153:1679–1686. [PMC free article] [PubMed]
9. Fukuchi K, Pham D, Hart M, Li L, Lindsey JR. Amyloid-beta deposition in skeletal muscle of transgenic mice: possible model of inclusion body myopathy. Am J Pathol. 1998;153:1687–1693. [PMC free article] [PubMed]
10. Sugarman MC, Yamasaki TR, Oddo S, et al. Inclusion body myositis-like phenotype induced by transgenic overexpression of bAPP in skeletal muscle. Proc Natl Acad Sci U S A. 2002;99:6334–6339. [PMC free article] [PubMed]
11. Askanas V, Engel WK, McFerrin J, Vattemi G. Transthyretin Val122Ile, accumulated Aβ and inclusion-body myositis aspects in cultured muscle. Neurology. 2003;22:61–257. [PubMed]
12. Klein WL. ADDLs and protofibrils: the missing links? Neurobiol Aging. 2002;23:231–235. [PubMed]
13. Walsh DM, Klyubin I, Fadeeva JV, et al. Naturally secreted oligomers of amyloid-β protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416:535–539. [PubMed]
14. Dahlgren KN, Manelli AM, Stine WB, Jr, Baker LK, Krafft GA, LaDu MJ. Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J Biol Chem. 2002;277:32046–32053. [PubMed]
15. De Felice FG, Vieira MN, Saraiva LM, et al. Targeting the neurotoxic species in Alzheimer’s disease: inhibitors of Abeta oligomerization. FASEB J. 2004;18:1366–1372. [PubMed]
16. Watson D, Castano E, Kokjohn TA, et al. Physicochemical characteristics of soluble oligomeric Abeta and their pathologic role in Alzheimer’s disease. Neurol Res. 2005;27:869–881. [PubMed]
17. Banwell BL, Engel AG. αB-crystallin immunolocalization yields new insights into inclusion body myositis. Neurology. 2000;54:1033–1041. [PubMed]
18. Karpati G, Hohlfeld R. Biologically stressed muscle fibers in sporadic IBM: a clue for the enigmatic etiology? Neurology. 2000;14:54–1020. [PubMed]
19. Derham BK, Harding JJ. Alpha-crystallin as a molecular chaperone. Prog Retin Eye Res. 1999;18:463–509. [PubMed]
20. Yu S, MacRae TH. The small heat shock proteins and their role in human disease. FEBS Journal. 2005;272:2613–2627. [PubMed]
21. Askanas V, Engel WK. Cultured normal and genetically abnormal human muscle. In: Rowland LP, Di Mauro S, editors. The Handbook of Clinical Neurology, Myopathies. Vol. 18. Amsterdam; North Holland: 1992. pp. 85–116.
22. Meng L, Mohan R, Kwok BH, Elofsson M, Sin N, Crews CM. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci U S A. 1999;96:10403–10408. [PMC free article] [PubMed]
23. Vattemi G, Engel WK, McFerrin J, Askanas V. Cystatin C colocalizes with amyloid-beta and coimmunoprecipitates with amyloid-beta precursor protein in sporadic inclusion-body myositis muscles. J Neurochem. 2003;85:1539–1546. [PubMed]
24. Vattemi G, Engel WK, McFerrin J, Askanas V. Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle. Am J Pathol. 2004;164:1–7. [PMC free article] [PubMed]
25. Wojcik S, Engel WK, McFerrin J, Askanas V. Myostatin is increased and complexes with amyloid-beta within sporadic inclusion-body myositis muscle fibers. Acta Neuropathol (Berl) 2005;110:173–177. [PubMed]
26. Cottrell BA, Galvan V, Banwait S, et al. A pilot proteomic study of amyloid precursor interactors in Alzheimer’s disease. Ann Neurol. 2005;58:277–289. [PMC free article] [PubMed]
27. Raman B, Ban T, Sakai M, et al. αB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid-β peptide and beta2 microglobulin. Biochem J. 2005;392:573–581. [PMC free article] [PubMed]
28. Stege GJ, Renkawek K, Overkamp PS, et al. The molecular chaperone alphaB-crystallin enhances amyloid beta neurotoxicity. Biochem Biophys Res Commun. 1999;262:152–156. [PubMed]
29. Boros S, Kamps B, Wunderink L, de Bruijin W, de Jong WW, Boelens WC. Transglutaminase catalyzes differential crosslinking of small heat shock proteins and amyloid-β FEBS Letters. 2004;576:57–62. [PubMed]
30. Vicart P, Caron A, Guicheney P, et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet. 1998;20:92–95. [PubMed]
31. Sanbe A, Osinska H, Villa C, et al. Reversal of amyloid-induced heart disease in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A. 2005;102:13592–13597. [PMC free article] [PubMed]
32. Ito H, Kamei K, Iwamoto I, et al. Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and alphaB-crystallin to aggresomes. J Biochem (Tokyo) 2002;131:593–603. [PubMed]
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...