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

George Perry, Hanno Roder, Akihiko Nunomura, Atsushi Takeda, Avi L. Friedlich, Xiongwei Zhu, Arun K. Raina, Nikki Holbrook, Sandra L. Siedlak, Peggy L.R. Harris, Mark A. Smith

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Abstract

RESPONSES to increased oxidative stress may be the common mechanism responsible for the varied cytopathology of Alzheimer disease (AD). A possible link in support of this hypothesis is that one of the most striking features of AD, the abnormal accumulation of highly phosphorylated τ and neurofilament proteins, may be brought about by extracellular receptor kinase (ERK) whose activation is a common response to oxidative stress. In this study, we demonstrate that activated ERK is specifically increased in the same vulnerable neurons in AD that are the site of oxidative damage and abnormal phosphorylation. These findings suggest that ERK dysregulation, likely resulting from oxidative stress, could play an important role in the increased phosphorylation of cytoskeletal proteins observed in AD.

Original languageEnglish
Pages (from-to)2411-2415
Number of pages5
JournalNeuroReport
Volume10
Issue number11
DOIs
Publication statusPublished - 1999 Aug 2

Keywords

  • Alzheimer disease
  • ERK2
  • MAP kinase
  • PHFτ
  • Phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

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    Perry, G., Roder, H., Nunomura, A., Takeda, A., Friedlich, A. L., Zhu, X., Raina, A. K., Holbrook, N., Siedlak, S. L., Harris, P. L. R., & Smith, M. A. (1999). Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation. NeuroReport, 10(11), 2411-2415. https://doi.org/10.1097/00001756-199908020-00035