The association between heat shock protein 27 (Hsp27) and hyperphosphorylated tau has gained attention for more than a decade, but it has never been explored in vivo. In the present study, we found that tau phosphorylated at S396/404 (PHF-1) and S262 sites was significantly increased in the cerebellum of Hsp27 transgenic mice, which was concomitant with increased glycogen synthase kinase-3β (GSK3β) phosphorylated at Y216 and decreased GSK3β phosphorylated at S9. Neither 70-kDa ribosomal protein S6 kinase (p70S6K; total p70S6K, p70S6K at T389, and p70S6K at T421/S424) nor protein phosphatase PP2A (total PP2A, PP2A at Y307, methylated or demethylated PP2A) was changed. This suggests that the increased tau phosphorylation at S396/404 and S262 sites may be induced by Hsp27 through enhancement of GSK3β activity in the mouse cerebellum.
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