title: ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro.
abstract: 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.
authors.affiliation: Département de Psychiatrie et Neurosciences, Faculté de médecine, Université Laval, Québec, Quebec, Canada; Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Quebec, Canada.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Noël
authors.affiliation: Département de Psychiatrie et Neurosciences, Faculté de médecine, Université Laval, Québec, Quebec, Canada; Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Quebec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poitras
authors.affiliation: Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Quebec, Canada.
authors.forename: Jacinthe
authors.initials: J
authors.lastname: Julien
authors.affiliation: Département de Psychiatrie et Neurosciences, Faculté de médecine, Université Laval, Québec, Quebec, Canada; Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Quebec, Canada.
authors.forename: Franck R
authors.initials: FR
authors.lastname: Petry
authors.affiliation: Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Quebec, Canada.
authors.forename: Françoise
authors.initials: F
authors.lastname: Morin
authors.affiliation: CRCHU de Québec, Axe Oncologie, Québec, Quebec, Canada; Centre de Recherche sur le Cancer de l'Université Laval, CRCHU de Québec, Québec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Charron
authors.affiliation: Département de Psychiatrie et Neurosciences, Faculté de médecine, Université Laval, Québec, Quebec, Canada; Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Quebec, Canada. Electronic address: emmanuel@planel.org.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000628:therapy; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D006979:Hyperthermia, Induced; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: ERK1/2; Hyperthermia; Hypothermia; MAPK; MEK1/2; PD0325901; PD184161; PD98059; SH-SY5Y; Tau phosphorylation