Oxidative stress induces dephosphorylation of tau in rat brain primary neuronal cultures

Oxidative stress and free radical damage have been implicated in the neurodegenerative changes characteristic of several neurodegenerative diseases, including Alzheimer's disease. There is experimental evidence that the neurotoxicity of beta-amyloid is mediated via free radicals, and as the deposition of beta-amyloid apparently precedes the formation of paired helical filaments (PHF) in Alzheimer's disease, we have investigated whether subjecting primary neuronal cultures to oxidative stress induces changes in the phosphorylation state of the principal PHF protein tau that resemble those found in PHF-tau. Contrary to causing an increase in tau phosphorylation, treatment of neurones with hydrogen peroxide caused a dephosphorylation of tau and so we conclude that oxidative stress is not the direct cause of tau hyperphosphorylation and hence of PHF formation.