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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Univ Sydney, Prince Wales Med Res Inst, Sydney, NSW 2006, Australia
Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia
Univ New S Wales, Sydney, NSW, AustraliaUniv Sydney, Prince Wales Med Res Inst, Sydney, NSW 2006, Australia
Loy, Clement T.
Schofield, Peter R.
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Univ Sydney, Prince Wales Med Res Inst, Sydney, NSW 2006, Australia
Univ New S Wales, Sydney, NSW, AustraliaUniv Sydney, Prince Wales Med Res Inst, Sydney, NSW 2006, Australia
Schofield, Peter R.
Kwok, John B. J.
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Univ Sydney, Prince Wales Med Res Inst, Sydney, NSW 2006, Australia
Univ New S Wales, Sydney, NSW, AustraliaUniv Sydney, Prince Wales Med Res Inst, Sydney, NSW 2006, Australia