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Mini-Reviews in Medicinal Chemistry

Author(s): Neha Chauhan, Swati Paliwal, Smita Jain, Kanika Verma, Sarvesh Paliwal and Swapnil Sharma*

DOI: 10.2174/1389557522666220420094317

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GSK-3β and its Inhibitors in Alzheimer's Disease: A Recent Update

Page: [2881 - 2895] Pages: 15

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Abstract

Alzheimer’s disease (AD) is an emerging major health and socioeconomic burden worldwide. It is characterized by neuronal loss, memory loss and cognitive impairment in the aging population. Despite several scientific advancements over the past five decades, the underlying molecular mechanism of the disease progression is yet unknown. Glycogen synthase kinase-3β (GSK-3β) has huge implications on the brain function, causing molecular pathologies, neuronal damage and impairment of brain performance in AD. It is one of the key players in signaling pathways for normal brain functioning and a critical molecular link between amyloid-beta (Aβ) and tau neurofibrillary tangles (NFTs). GSK-3β activation is driven by phosphorylation of tau(τ) protein which results in disruption of neuronal synaptic activities and the formation of neuronal plaques. Although the accumulation of Aβ plaques and intracellular tangles of hyperphosphorylated tau protein has been well established as neuropathological hallmarks of the disease, the molecular mechanism has not been unraveled. This review focuses on the role of GSK-3β in the molecular mechanisms participating in the manifestation and progression of AD. The review also suggests that GSK-3β inhibitors can be used as potential therapeutic targets for amelioration of AD.

Keywords: Alzheimer’s disease, glycogen synthase kinase-3, neurodegenerative diseases, neurofibrillary tangles, tau protein, amyloid-beta.

Graphical Abstract

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