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Role of GSK‐3β in Alzheimer's disease pathology
Author(s) -
Planel Emmanuel,
Sun Xiaoyan,
Takashima Akihiko
Publication year - 2002
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10100
Subject(s) - gsk 3 , presenilin , hyperphosphorylation , kinase , neuroscience , gsk3b , alzheimer's disease , glycogen synthase , protein kinase a , biology , tau protein , programmed cell death , amyloid precursor protein , cyclin dependent kinase 5 , disease , microbiology and biotechnology , phosphorylation , medicine , biochemistry , mitogen activated protein kinase kinase , apoptosis
Glycogen synthase kinase 3β (GSK‐3β) is an important regulatory kinase involved in multiple processes such as metabolic control, embryonic development, cell death, and oncogenesis. It has been found to interact with many molecules associated with Alzheimer's disease (AD) such as the microtubule‐associated protein tau, presenilin 1, the amyloid‐β peptide, the amyloid precursor protein, and acetylcholine. Furthermore, GSK‐3β might be involved in brain aging and longevity. As GSK‐3β is associated with so many components of AD pathology, we review the current data on the role of this kinase in tau hyperphosphorylation, then look at its association with AD‐related molecules and pathways, and finally discuss its involvement in cell death and aging. We attempt to integrate all these data to arrive at the proposition that GSK‐3β is a pivotal molecule in the evolution of AD and that developing drugs directed at this kinase might prove to be beneficial in the treatment of this devastating disease. Drug Dev. Res. 56:491–510, 2002. © 2002 Wiley‐Liss, Inc.