title: Hyperphosphorylation of microtubule-associated protein tau in senescence-accelerated mouse (SAM).
abstract: Tau is a neuronal microtubule-associated protein found predominantly on axons. Tau phosphorylation regulates both normal and pathological functions of this protein. Hyperphosphorylation impairs the microtubule binding function of tau, resulting in the destabilization of microtubules in brain, ultimately leading to the degeneration of the affected neurons. Numerous serine/threonine kinases, including GSK-3beta and Cdk5 can phosphorylate tau. SAMR1 and SAMP8 are murine strains of senescence. We show an increase in hyperphosphorylated forms of tau in SAMP8 (senescent mice) in comparison with resistant strain SAMR1. Moreover, an increase in Cdk5 expression and activation is described but analysis of GSK3beta isoforms failed to show differences in SAMP8 in comparison to age-matched SAMR1. In conclusion, tau hyperphosphorylation occurs in SAMP-8 (early senescent) mice, indicating a link between aging and tau modifications in this murine model.
authors.affiliation: Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028 Barcelona, Spain.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Canudas
authors.forename: Javier
authors.initials: J
authors.lastname: Gutierrez-Cuesta
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Rodríguez
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
authors.forename: Francesc X
authors.initials: FX
authors.lastname: Sureda
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
mesh_terms: D000375:Aging; D000818:Animals; D001369:Axons / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D016922:Cellular Senescence; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms; D014018:Tissue Distribution; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D014404:Tubulin; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5