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Titolo:
Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3 beta conditional transgenic mice
Autore:
Lucas, JL; Hernandez, F; Gomez-Ramos, P; Moran, MA; Hen, R; Avila, J;
Indirizzi:
Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain Univ Autonoma Madrid Madrid Spain E-28049 o Ochoa, E-28049 Madrid, Spain Univ Autonoma Madrid, Fac Med, Dept Morfol, Madrid 28049, Spain Univ Autonoma Madrid Madrid Spain 28049 Dept Morfol, Madrid 28049, Spain Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA Columbia Univ New York NY USA 10032 obiol & Behav, New York, NY 10032 USA
Titolo Testata:
EMBO JOURNAL
fascicolo: 1-2, volume: 20, anno: 2001,
pagine: 27 - 39
SICI:
0261-4189(20010115)20:1-2<27:DNBTHA>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLYCOGEN-SYNTHASE KINASE-3; PAIRED HELICAL FILAMENTS; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; MAMMALIAN-CELLS; NEUROFIBRILLARY TANGLES; MUTANT PRESENILIN-1; HIPPOCAMPAL-NEURONS; GENE-EXPRESSION; PHOSPHORYLATION;
Keywords:
Alzheimer's disease; beta-catenin; conditional transgenic mice; GSK-3 beta; tau phosphorylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Avila, J Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain Univ Autonoma Madrid Madrid Spain E-28049 E-28049 Madrid, Spain
Citazione:
J.L. Lucas et al., "Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3 beta conditional transgenic mice", EMBO J, 20(1-2), 2001, pp. 27-39

Abstract

Glycogen synthase kinase-3 beta (GSK-3 beta) has been postulated to mediate Alzheimer's disease tau hyperphosphorylation, beta -amyloid-induced neurotoxicity and presenilin-1 mutation pathogenic effects. By using the tet-regulated system we have produced conditional transgenic mice overexpressing GSK-3 beta in the brain during adulthood while avoiding perinatal lethality due to embryonic transgene expression. These mice show decreased levels of nuclear beta -catenin and hyperphosphorylation of tau in hippocampal neurons, the latter resulting in pretangle-like somatodendritic localization of tau, Neurons displaying somatodendritic localization of tau often show abnormal morphologies and detachment from the surrounding neuropil, Reactive astrocytosis and microgliosis were also indicative of neuronal stress and death. This was further confirmed by TUNEL and cleaved caspase-3 immunostainingof dentate gyrus granule cells. Our results demonstrate that in vivo overexpression of GSK-3 beta results in neurodegeneration and suggest that thesemice can be used as an animal model to study the relevance of GSK-3 beta deregulation to the pathogenesis of Alzheimer's disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 19:29:26