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 mol ecular studies all now point to a functional relationship between alpha B-c rystallin and intermediate filaments. alpha B-crystallin accumulation marks reactive astrocytes in general in a wide variety of disorders and specific ally intermediate filament-based glial inclusion bodies such as Rosenthal f ibres found in astrocytes in Alexander's disease. In vitro, alpha B-crystal lin expression suppresses intermediate filament aggregation and can prevent or reverse experimentally induced glial inclusion body formation. Converse ly. dysregulation of glial fibrillary acidic protein expression in vivo res ults in Rosenthal fibre formation and upregulation of endogenous alpha B-cr ystallin expression. These data and those from studies recently carried out on other tissues strongly suggest that one function of this small heat sho ck protein is to modulate intermediate filament organization under conditio ns of physiological stress and neurodegenerative disease.