title: Regulation of tau proteolysis by phosphatases.
abstract: One pathological hallmark of Alzheimer's disease is the accumulation of highly phosphorylated tau. Since tau phosphorylation inhibits its proteolysis, we examined the impact of endogenous phosphatase activities on tau proteolysis by homogenization of cultured cells and 3xTg-AD mouse brain followed by incubation with or without phosphatase inhibitors. Incubation without phosphatase inhibitors significantly increased tau immunoreactivity against antibody C3 (which reacts with tau truncated at D421), and increased the generation of tau breakdown products. These changes were augmented by lithium treatment and inhibited by constitutively active GSK3β. These findings underscore that tau proteolysis is regulated by a balance of kinase and phosphatase activities.
authors.affiliation: University of Massachusetts Lowell, Department of Biological Sciences, Center for Cellular Neurobiology and Neurodegeneration Research, One University Avenue, Lowell, MA 01854, USA.
authors.forename: Sangmook
authors.initials: S
authors.lastname: Lee
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D008822:Mice, Transgenic; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D059748:Proteolysis; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D010744:Phosphoric Monoester Hydrolases