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GSK-3 Inhibitors: A New Class of Drugs for Alzheimer’s Disease Treatment

[ Vol. 22 , Issue. 15 ]

Author(s):

Dilipkumar Pal, Souvik Mukherjee, In-Ho Song and Satish B. Nimse*   Pages 1725 - 1737 ( 13 )

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.

Keywords:

Alzheimer's disease, GSK-3, GSK-3 inhibitors, Tau, β-amyloid, neurodegenerative diseases, protein kinase.

Affiliation:

Department of Pharmaceutical Sciences, Guru Ghasidas Viswavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, Department of Pharmaceutical Sciences, Guru Ghasidas Viswavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200702, Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200702

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