Small heat shock proteins participate in the regulation of cellular aggregates of misfolded protein

Molecular chaperones participate in folding of many proteins and several families are known to exist in mammalian cells including the small heat shock protein (sHSP) family. sHSPs have a molecular mass of 15-30 kDa and are known to be induced and phosphorylated in response to various stimuli. There are several reports describing the correlation between sHSPs and degenerative diseases. We have been reported that Hsp27 and alpha B-crystallin were recruited to aggresome when cells were treated with proteasome inhibitors. Expression of Hsp27 suppresses the cell death induced by expression of expanded polyglutamine via down regulation of the oxidative stress pathway. Recently, a missense mutation in alpha B-crystallin, R120G, has been found in a French family suffering from desmin-related myopathy. Moreover, transgenic mice expressing R120G alpha B-crystallin exhibit symptoms similar to desmin-related myopathy. We recently examined the interaction of R120G alpha B-crystallin and Hsp27 in mammalian cells and found that expression of R120G alpha B-crystallin caused formation of inclusion bodies and co-expression of Hsp27 inhibited this formation of inclusion bodies. Clarification of physiological roles of sHSPs in degenerative diseases may lead to the development of new therapy.