Abstract
Filamentous tau-positive protein inclusions in neurons and glia are prominent features of a number of neurodegenerative disorders termed tauopathies. These inclusions are further characterized by the presence of heat shock proteins (HSPs). The group of small HSPs, namely, HSP27 and alphaB-crystallin, interact with the cytoskeleton, bind to nonnative proteins, and prevent their aggregation after stress. To further investigate their contribution to neurodegenerative diseases, we have analyzed the association of HSP27 with pathological lesions of tauopathies. Microarray and immunoblot analysis revealed that HSP27 is enhanced at the mRNA and protein levels in affected brains, and that it is associated with astrocytic pathology. The upregulation of HSP27 in tauopathies with gial pathology implies distinct mechanisms for glial and neuronal cells. This was sustained by cell culture studies, demonstrating that the small HSPs are specifically and prominently expressed in unstressed astrocytes and not in neurons and in neurons remained at a rather low level even after stress situations.