title: Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons.
abstract: In Alzheimer's disease, tau protein becomes hyperphosporylated, which can contribute to neuronal degeneration. However, the implicated protein kinases are still unknown. Now we report that lithium (an inhibitor of glycogen synthase kinase-3) causes tau dephosphorylation at the sites recognized by antibodies Tau-1 and PHF-1 both in cultured neurons and in vivo in rat brain. This is consistent with a major role for glycogen synthase kinase-3 in modifying proline-directed sites on tau protein within living neurons under physiological conditions. Lithium also blocks the Alzheimer's disease-like proline-directed hyperphosphorylation of tau protein which is observed in neurons treated with a phosphatase inhibitor. These data raise the possibility of using lithium to prevent tau hyperphosphorylation in Alzheimer's disease.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Muñoz-Montaño
authors.forename: F J
authors.initials: FJ
authors.lastname: Moreno
authors.forename: J
authors.initials: J
authors.lastname: Avila
authors.forename: J
authors.initials: J
authors.lastname: Diaz-Nido
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D007701:Kinetin; D008094:Lithium / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011392:Proline / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D051381:Rats; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D011687:Purines; D016875:tau Proteins; D019319:Okadaic Acid; C090046:olomoucine; D011392:Proline; D008094:Lithium; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3; D007701:Kinetin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one