Alzheimer's Disease (AD) is the most prevalent form of age-related dementia. Even though a century has passed since the discovery of AD, the exact cause of the disease still remains unknown. As a result, this poses a major hindrance in developing effective therapies for treating AD. Glycogen synthase kinase-3 (GSK-3) is one of the kinases that has been investigated recently as a potential therapeutic target for the treatment of AD. It is also known as human tau protein kinase and is a proline-directed serine-threonine kinase. Since dysregulation of this kinase affects all the major characteristic features of the disease, such as tau phosphorylation, amyloid formation, memory, and synaptic function, it is thought to be a major player in the pathogenesis of AD. In this review, we present the most recent information on the role of this kinase in the onset and progression of AD, as well as significant findings that identify GSK-3 as one of the most important targets for AD therapy. We further discuss the potential of treating AD by targeting GSK-3 and give an overview of the ongoing studies aimed at developing GSK-3 inhibitors in preclinical and clinical investigations.
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Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R ChinaFudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
Zhang, Peng
Hu, Hai-Rong
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Fudan Univ, Sch Life Sci, Key Lab State Genet Engn, Shanghai 200433, Peoples R ChinaFudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
Hu, Hai-Rong
Huang, Zhao-Hui
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Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R ChinaFudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
Huang, Zhao-Hui
Lei, Jia-Yi
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Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R ChinaFudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
Lei, Jia-Yi
Chu, Yong
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Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R ChinaFudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
Chu, Yong
Ye, De-Yong
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Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R ChinaFudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China