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ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro

Anastasia Noël1, Isabelle Poitras1, Jacinthe Julien2

  • 1Département de Psychiatrie et Neurosciences, Faculté de médecine, Université Laval, Québec, Quebec, Canada; Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Quebec, Canada.

Neurobiology of Aging
|December 11, 2014
PubMed

Insights

Extracellular signal-regulated kinases 1/2 (ERK1/2) do not appear to play a significant role in tau protein phosphorylation in Alzheimer's disease models. Studies show inhibiting or activating ERK1/2 did not alter tau phosphorylation levels.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Alzheimer's disease involves intracellular tau protein aggregates due to hyperphosphorylation.
  • Dysregulated kinase and phosphatase activity contributes to tau hyperphosphorylation.
  • Extracellular signal-regulated kinases 1/2 (ERK1/2) are implicated in early Alzheimer's disease stages and considered a therapeutic target.

Purpose of the Study:

  • To investigate the in vivo role of ERK1/2 in tau phosphorylation.
  • To determine if ERK1/2 inhibition or activation affects tau phosphorylation under physiological and induced conditions.

Main Methods:

  • Pharmacologic inhibition of ERK1/2 in mice and SH-SY5Y cells.
  • Induction of tau hyperphosphorylation via hypothermia and ERK1/2 activation via hyperthermia.
  • Analysis of tau phosphorylation in Mek1-/- mice with inhibited ERK1/2.

Main Results:

  • Pharmacologic ERK1/2 inhibition did not alter basal or hypothermia-induced phospho-tau levels.
  • Hyperthermia-induced ERK1/2 activation did not correlate with increased tau phosphorylation.
  • Inhibition of ERK1/2 in Mek1-/- mice did not affect tau phosphorylation.

Conclusions:

  • The findings do not support the involvement of ERK1/2 in tau phosphorylation under physiological conditions.
  • ERK1/2 may not be a suitable therapeutic target for reducing tau hyperphosphorylation in Alzheimer's disease.
Keywords:
ERK1/2HyperthermiaHypothermiaMAPKMEK1/2PD0325901PD184161PD98059SH-SY5YTau phosphorylation

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