Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer's disease

• Published in: Current pharmaceutical design Vol. 16; no. 25; p. 2790
• Main Authors: Medina, Miguel, Avila, Jesús
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.08.2010
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - enzymology; Alzheimer Disease - pathology; Animals; Drug Delivery Systems - methods; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - metabolism; Humans; Lithium Compounds - pharmacology; Models, Biological; Nerve Degeneration - drug therapy; Nerve Degeneration - enzymology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use
• ISSN: 1873-4286
• DOI: 10.2174/138161210793176581

Originally discovered because of its role in the regulation of glucose metabolism, Glycogen Synthase Kinase-3 (GSK-3) it is now recognised as a crucial player in a diverse series of cellular processes involved in Alzheimer's disease (AD) pathology. Besides having been identified as the major tau protein kinase, GSK-3 mediates Aβ neurotoxicity, plays an essential role in synaptic plasticity and memory, might be involved in Aβ formation, and it has an important role in inflammation and neuronal survival, all key features of AD neuropathology. Moreover, AD was one of the earliest disorders linked to GSK-3 dysfunction. Thus, the discovery of small molecule GSK-3 inhibitors has attracted significant attention to the protein both as therapeutic target for the therapeutic intervention in neurodegenerative diseases as well as a means to understand the molecular basis of these disorders.