Pin1 affects Tau phosphorylation in response to Aβ oligomers

We show that in hippocampal cultured neurons, dephosphorylation of peptidyl-prolyl cis-trans isomerase Pin1 on Ser16 is occurring during the early stages of exposure to A beta (1-42) oligomers. This occurrence, resulting in Pin1 activation, is paralleled by Tau(Thr231) dephosphorylation, probably due to Pin1-mediated Tau isomerisation. Indeed, in the presence of the specific Pin1 inhibitor juglone, A beta-induced Tau(Thr231) dephosphorylation is prevented. The involvement of protein phosphatase 2A (PP2A) in dephosphorylation of isomerised Tau is shown by the co-treatment of neurons with A beta (1-42) and okadaic acid, a PP2A inhibitor, leading to Tau(Thr231) hyperphosphorylation. We also report the modulation, via Pin1, of Ser199, Ser396, Ser400 and Ser404 phosphorylation state in response to A beta treatment. Taken together, these data suggest for the first time that an early Pin1 response might be transiently evoked by A beta 1-42 oligomers, preventing Tau hyperphosphorylation. This evidence highlights the role of Pin1 as Tau phosphorylation modulator during Alzheimer onset. (C) 2009 Elsevier Inc. All rights reserved.