Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis

Cristiana Atzori, Bernardino Ghetti, Roberto Piva, Anu N. Srinivasan, Paolo Zolo, Marie Bernadette Delisle, Suzanne S. Mirra, Antonio Migheli

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Abstract

JNK and p38, two members of the MAP kinase family, are strongly induced by various stresses including oxidative stress and have been involved in regulation of apoptosis. As both kinases phosphorylate tau protein in vitro, we have investigated their immunohistochemical localization in a group of neurodegenerative diseases characterized by intracellular deposits of hyperphosphorylated tau. Cases included Alzheimer disease, Pick disease, progressive supranuclear palsy, corticobasal degeneration, Gerstmann-Sträussler-Scheinker disease-Indiana kindred, and frontotemporal dementia with parkinsonism linked to chromosome 17. In all tissue samples, strong immunoreactivity for both MAP kinases was found in the same neuronal or glial cells that contained tau-positive deposits. By double immunohistochemistry, JNK and p38 colocalized with tau in the inclusions. Analysis of apoptosis-related changes (DNA fragmentation, activated caspase-3) showed that the expression of JNK and p38 was unrelated to activation of an apoptotic cascade. Our data indicate that phospho-JNK and phosphop38 are associated with hyperphosphorylated tau in a variety of abnormal tau inclusions, suggesting that these kinases may play a role in the development of degenerative diseases with tau pathology.

Original languageEnglish (US)
Pages (from-to)1190-1197
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume60
Issue number12
DOIs
StatePublished - Jan 1 2001

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Keywords

  • Apoptosis
  • JNK
  • MAP kinase
  • p38
  • Phosphorylation
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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