The p38 pathway is activated in Pick disease and progressive supranuclear palsy: A mechanistic link between mitogenic pathways, oxidative stress, and tau

Anthony W. Hartzler, Xiongwei Zhu, Sandra L. Siedlak, Rudolph J. Castellani, Jesus Avilá, George Perry, Mark A. Smith

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

In Pick disease and progressive supranuclear palsy (PSP), accumulations of phosphorylated τ are associated with oxidative stress, although the mechanism linking these features remains unknown. However, we suspected that the oxidative stress-induced activation of mitogen-activated protein kinases might lead to τ phosphorylation and accumulation as characteristic inclusion bodies. To test this notion, we investigated whether the activation of mitogen-activated protein kinases is involved in the pathogenesis of Pick disease and PSP. Our results show that the lesions of both Pick disease and PSP are associated with the activation of the p38 pathway (phospho-MKK6 and phospho-p38), one of the best characterized of the mitogen-activated protein kinase pathways. Based on these findings, we propose that the phosphorylation of τ is a direct consequence of the oxidative stress-induced activation of mitogen-activated protein kinases, including p38.

Original languageEnglish (US)
Pages (from-to)855-859
Number of pages5
JournalNeurobiology of Aging
Volume23
Issue number5
DOIs
StatePublished - Sep 1 2002
Externally publishedYes

Keywords

  • Cytoskeleton
  • Immunocytochemistry
  • MAP kinase
  • MKK6
  • Neurodegeneration
  • Neurofibrillary tangles
  • Oxidative stress
  • Phosphorylated tau
  • Pick disease
  • Progressive supranuclear palsy
  • Signal transduction
  • p38

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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