Binding of Tau to Heat Shock Protein 27 Leads to Decreased Concentration of Hyperphosphorylated Tau and Enhanced Cell Survival

Pathological hyperphosphorylated tau is the principal component of paired helical filaments, a pathological hallmark of Alzheimer disease (AD) and a strong candidate for a neurotoxic role in AD and other neurodegenerative disorders. Here we show that heat shock protein 27 (Hsp27) preferentially binds pathological hyperphosphorylated tau and paired helical filaments tau directly but not non-phosphorylated tau. The formation of this complex altered the conformation of pathological hyperphosphorylated tau and reduced its concentration by facilitating its degradation and dephosphorylation. Moreover, Hsp27 rescues pathological hyperphosphorylated tau-mediated cell death. Therefore, Hsp27 is likely to provide a neuroprotective effect in AD and other tauopathies.