Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation

RESPONSES to increased oxidative stress may be the common mechanism respons ible for the varied cytopathology of Alzheimer disease (AD). A possible lin k in support of this hypothesis is that one of the most striking features o f AD, the abnormal accumulation of highly phosphorylated tau and neurofilam ent proteins, may be brought about by extracellular receptor kinase (ERK) w hose activation is a common response to oxidative stress. In this study, we demonstrate that activated ERK is specifically increased in the same vulne rable neurons in AD that are the site of oxidative damage and abnormal phos phorylation. These findings suggest that ERK dysregulation, likely resultin g from oxidative stress, could play an important role in the increased phos phorylation of cytoskeletal proteins observed in AD. NeuroReport 10:2411-24 15 (C) 1999 Lippincott Williams & Wilkins.