Title:GSK-3 Inhibitors: A New Class of Drugs for Alzheimer’s Disease Treatment
Volume: 22
Issue: 15
Author(s): Dilipkumar Pal, Souvik Mukherjee, In-Ho Song and Satish B. Nimse*
Affiliation:
- Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200702,Korea
Keywords:
Alzheimer's disease, GSK-3, GSK-3 inhibitors, Tau, β-amyloid, neurodegenerative diseases, protein kinase.
Abstract: 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 Ki
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.
