title: The sphingosine-1-phosphate receptor 1 agonist SEW2871 reduces Tau-Ser262 phosphorylation in rat hippocampal slices.
abstract: Recent studies indicate that Tau phosphorylation can be modulated by the compound FTY720-P, a global sphingosine-1-phosphate receptor (S1PR) agonist. The present work compared the effects of more selective S1PR agonists on Tau properties, using rat hippocampal slices as model system. Whereas Tau phosphorylation was not modified by the S1PR3 agonist CYM5541, Tau-Ser262 phosphorylation was significantly decreased by treatment with the S1PR1 agonist SEW2871. This effect appears to be quite restricted, as no changes in phosphorylation were elicited by the agonist on Tau-Ser199/202, Tau-Ser396 and Tau-Ser404 residues. In terms of molecular mechanisms, it is proposed that SEW2871-induced reduction of Tau-Ser262 phosphorylation depends on AMP-activated protein kinase alpha (AMPKα) inactivation via a pathway requiring AMPKα dephosphorylation at Thr172 by the protein phosphatase 2A (PP2A).
authors.affiliation: Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: St-Cyr Giguère
authors.affiliation: Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Attiori Essis
authors.affiliation: Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: Laure
authors.initials: L
authors.lastname: Chagniel
authors.affiliation: Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Germain
authors.affiliation: Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Cyr
authors.affiliation: Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada. Electronic address: Guy.Massicotte@uqtr.ca.
authors.forename: Guy
authors.initials: G
authors.lastname: Massicotte
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002491:Central Nervous System Agents; D007555:Isoxazoles; C489131:Mapt protein, rat; C000621670:N,N-dicyclohexyl(5-cyclopropylisoxazol-3-yl)carboxamide; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; C578616:S1PR1 protein, rat; C578617:S1PR3 protein, rat; C503964:SEW2871; D000081025:Sphingosine-1-Phosphate Receptors; D013876:Thiophenes; D016875:tau Proteins; D055372:AMP-Activated Protein Kinases; D054648:Protein Phosphatase 2
keywords: AMPK; Hippocampus; S1P receptors; Tau phosphorylation