New insights into the role of glycogen synthase kinase-3 in Alzheimer's disease.

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.

• 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)

Chemical References

• Amyloid beta-Protein Precursor
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3
• Amyloid Precursor Protein Secretases

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