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

• DOI: 10.1016/j.neurobiolaging.2014.11.005
• Publication Date: 2014-11-16T22:35:50Z
• Authors: Anastasia Noël; Isabelle Poitras; Jacinthe Julien; Franck R. Petry; Françoise Morin; Jean Charron; Emmanuel Planel
• Keywords: Hyperphosphorylation; Tau protein; Dephosphorylation

Alzheimer's disease is characterized by the deposition of intracellular aggregates of hyperphosphorylated tau protein. Tau hyperphosphorylation has been attributed in part to the deregulation of kinases and phosphatases activities. Extracellular signal regulated-kinases 1/2 (ERK1/2) were reported to be activated in the first stages of Alzheimer's disease and were proposed as a potential therapeutic target. However, although the phosphorylation of tau by ERK1/2 has been demonstrated in cell-free system, it remains controversial in vivo. Here, we showed that pharmacologic inhibition of ERK1/2 in mice and SH-SY5Y cells did not reduce basal levels of phospho-tau or hypothermia-induced tau hyperphosphorylation. We also found that activating ERK1/2 by hyperthermia did not correlate with increased tau phosphorylation. Finally, ERK1/2 was inhibited, but tau phosphorylation was not altered in Mek1-/- mice. In conclusion, these results do not support the involvement of ERK1/2 in tau phosphorylation under physiological conditions.