The GSK3 hypothesis of Alzheimer's disease

C Hooper, R Killick, S Lovestone - Journal of neurochemistry, 2008 - Wiley Online Library
Journal of neurochemistry, 2008Wiley Online Library
J. Neurochem.(2008) 104, 1433–1439. 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 …
J. Neurochem. (2008) 104, 1433–1439.
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 β‐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.
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