The sphingosine-1-phosphate receptor 1 agonist SEW2871 reduces Tau-Ser262 phosphorylation in rat hippocampal slices
| Autor: | Guy Massicotte, Marc Germain, Laure Chagniel, Suzanne Attiori Essis, Michel Cyr, Frédéric St-Cyr Giguère |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Agonist medicine.medical_specialty medicine.drug_class Blotting Western Drug Evaluation Preclinical tau Proteins Thiophenes AMP-Activated Protein Kinases Hippocampus Rats Sprague-Dawley Tissue Culture Techniques Dephosphorylation 03 medical and health sciences Internal medicine mental disorders medicine Animals Amino Acid Sequence Protein Phosphatase 2 Phosphorylation Protein kinase A Receptor Sphingosine-1-Phosphate Receptors Molecular Biology S1PR1 S1PR3 Oxadiazoles Molecular Structure Chemistry General Neuroscience Isoxazoles Protein phosphatase 2 Cell biology Receptors Lysosphingolipid 030104 developmental biology Endocrinology Neurology (clinical) Central Nervous System Agents Developmental Biology |
| Zdroj: | Brain Research. 1658:51-59 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2017.01.014 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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