Small Heat Shock Proteins in Neurodegenerative Diseases.

The small heat shock proteins (sHSP) comprise 10 members in mammals where they are called the HspB proteins (HspB1-10). Like other HSP, the HspB proteins have chaperone activity in vitro. This activity is poorly characterized in vivo, however, many of these proteins protect cells against diverse stress and have been associated, in numerous studies, with protein conformation diseases. HspB proteins are upregulated in neurodegenerative disorders, including brain amyloidosis, and immunohistochemicalstudies showed that they are often trapped within proteininclusions that are formed in these diseases. Moreover, HspB proteins show a protective effect against protein aggregation and toxicity in cellular model of conformational diseases. Furthermore, mutations in four HspB proteins (HspB1, HspB4, HspB5 and HspB8) have been associated with neuromuscular and other protein conformation disorders. These observations constitute strong support for an important role of the HspB proteins in neurodegenerative disorders.