Abstract | INTRODUCTION:
Glycogen synthase kinase-3 (GSK-3) is recognized as a crucial player in many cellular functions and its activity is tightly controlled by complex mechanisms that are each dependent upon specific signaling pathways. Furthermore, GSK-3 dysfunction has been linked to a number of pathologies, including Alzheimer's disease (AD). In particular, the involvement of GSK-3 in several key pathophysiological pathways leading to AD and neurodegenerative diseases has placed this enzyme in a central position in this disorder. AREAS COVERED: This article offers a review of the relationship between GSK-3 and AD with a special focus on recent evidence showing a key role of GSK-3 activity in modulating cellular pathways controlling amyloid formation, especially through the control of β-site APP-cleaving enzyme 1 gene expression, as well as its role as a key regulator of neurogenesis. EXPERT OPINION:
GSK-3 appears to be a cellular nexus, integrating several signaling systems, including several second messengers and a wide selection of cellular stimulants. The next few years will certainly bring us further insights into the cellular functions of this fascinating enzyme and its potential as a therapeutic target in AD and other neurological disorders.
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Authors | Miguel Medina, Jesús Avila |
Journal | Expert opinion on therapeutic targets
(Expert Opin Ther Targets)
Vol. 18
Issue 1
Pg. 69-77
(Jan 2014)
ISSN: 1744-7631 [Electronic] England |
PMID | 24099155
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Amyloid beta-Protein Precursor
- Glycogen Synthase Kinase 3 beta
- Glycogen Synthase Kinase 3
- Amyloid Precursor Protein Secretases
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Topics |
- Alzheimer Disease
(enzymology)
- Amyloid Precursor Protein Secretases
(metabolism)
- Amyloid beta-Protein Precursor
(metabolism)
- Brain
(metabolism, physiopathology)
- Glycogen Synthase Kinase 3
(metabolism)
- Glycogen Synthase Kinase 3 beta
- Humans
- Neurogenesis
- Protein Processing, Post-Translational
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