title: The GSK3 hypothesis of Alzheimer's disease.
abstract: Glycogen synthase kinase 3 (GSK3) is a constitutively active, proline-directed serine/threonine kinase that plays a part in a number of physiological processes ranging from glycogen metabolism to gene transcription. GSK3 also plays a pivotal and central role in the pathogenesis of both sporadic and familial forms of Alzheimer's disease (AD), an observation that has led us to coin the 'GSK3 hypothesis of AD'. According to this hypothesis, over-activity of GSK3 accounts for memory impairment, tau hyper-phosphorylation, increased beta-amyloid production and local plaque-associated microglial-mediated inflammatory responses; all of which are hallmark characteristics of AD. If our 'GSK3 hypothesis of AD' is substantiated and GSK3 is indeed a causal mediator of AD then inhibitors of GSK3 would provide a novel avenue for therapeutic intervention in this devastating disorder.
authors: King's College London, MRC Centre for Neurodegenerative Research, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK.
authors: Claudie
authors: C
authors: Hooper
authors: Richard
authors: R
authors: Killick
authors: Simon
authors: S
authors: Lovestone
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology
chemical_list: D038362:Glycogen Synthase Kinase 3