4.4 Review

GSK-3 inhibitors: A New Class of Drugs for Alzheimer's Disease Treatment

Journal

CURRENT DRUG TARGETS
Volume 22, Issue 15, Pages 1725-1737

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389450122666210114095307

Keywords

Alzheimer's disease; GSK-3; GSK-3 inhibitors; Tau; beta-amyloid; neurodegenerative diseases; protein kinase

Funding

  1. Hallym University Research Fund [HRF-202012-009]

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Alzheimer's disease is a common form of dementia caused by cognitive function impairment, with research suggesting the involvement of GSK-3 in the hyper-phosphorylation of tau proteins, making it a potential target for AD treatment. Inhibitors of GSK-3 have received significant attention for their potential therapeutic applications in AD and other diseases.
Alzheimer's disease (AD), a chronic neurodegenerative disease, is the most common form of dementia that causes cognitive function impairment, including memory, thinking, and behavioral changes that ultimately lead to death. The overactivation of GSK-3, an enzyme from the proline/serine K-i(NS) family, has been associated with hyper-phosphorylation of tau proteins. The self-assembly of hyper-phosphorylated tau proteins to form tangles of straight and helical filaments is known to be involved in AD. Therefore, GSK-3 has been considered a potential target of novel drug discovery for AD treatment. Research on the development of GSK-3 inhibitors has received enormous attention from the vast scientific community because they are targeted for AD and other diseases, including type 2 diabetes, cancers, stroke, Parkinson's disease and bipolar disorder. Various drugs of both synthetic and natural origins have been designed to inhibit GSK-3 activity. However, there is a need to develop novel drug candidates that can selectively inhibit GSK-3. Hence, this review summarizes the potential of GSK-3 inhibitors for AD therapy and discusses the structure-activity relationship of current drug molecules and the potential problems associated with them.

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