Small heat shock proteins, the cytoskeleton, and inclusion body formation.
Since first being implicated in central nervous system disease 10 years ago, much has been learned concerning the regulation and function of the small heat shock protein alpha B-crystallin. Neuropathological, cellular and molecular studies all now point to a functional relationship between alpha B-crystallin and intermediate filaments. alpha B-crystallin accumulation marks reactive astrocytes in general in a wide variety of disorders and specifically intermediate filament-based glial inclusion bodies such as Rosenthal fibres found in astrocytes in Alexander's disease. In vitro, alpha B-crystallin expression suppresses intermediate filament aggregation and can prevent or reverse experimentally induced glial inclusion body formation. Conversely, dysregulation of glial fibrillary acidic protein expression in vivo results in Rosenthal fibre formation and upregulation of endogenous alpha B-crystallin expression. These data and those from studies recently carried out on other tissues strongly suggest that one function of this small heat shock protein is to modulate intermediate filament organization under conditions of physiological stress and neurodegenerative disease.
The National CJD Surveillance Unit, Western General Hospital, Edinburgh, UK.m.w.head@ed.ac.uk
M W
MW
Head
J E
JE
Goldman
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology; D003459:Crystallins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism; D051381:Rats
D015415:Biomarkers; D003459:Crystallins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C486114:Hspb1 protein, rat; D018832:Molecular Chaperones; D009363:Neoplasm Proteins