title: Possible role of tau protein kinases in pathogenesis of Alzheimer's disease.
abstract: Tau protein kinases (TPK) I and II were isolated as candidate enzymes responsible for the hyperphosphorylation observed in PHF-tau. Four phosphorylation sites of tau were identified for each kinase, accounting for most, but not all, of the major phosphorylation sites of PHF-tau. Immunostaining with anti-TPKI antibody indicated that this kinase is up-regulated in AD brain. Such up-regulation of TPKI and phosphorylatioin of tau were reproduced by treating cultured hippocampal cells with amyloid beta (Abeta) protein. In addition, we found that TPKI can phosphorylate and inactivate pyruvate dehydrogenase (PDH), which is expected to result in depletion of acetyl-CoA, a key substrate of acetyl choline synthesis. Indeed, when septum cells were treated with Abeta, the level of acetyl choline decreased dramatically.
authors.affiliation: Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo, Japan. scrtry@libra.ls.m-kagaku.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Imahori
authors.forename: M
authors.initials: M
authors.lastname: Hoshi
authors.forename: K
authors.initials: K
authors.lastname: Ishiguro
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: R
authors.initials: R
authors.lastname: Shiurba
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: A
authors.initials: A
authors.lastname: Takashima
authors.forename: T
authors.initials: T
authors.lastname: Uchida
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D051360:Cyclin-Dependent Kinase 5; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C079134:tau protein kinase II; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase