Insight γ-Secretase: Structure, Function, and Role in Alzheimer’s Disease

Author(s): Suvadeep Mal, Udita Malik, Dilipkumar Pal*, Abhishek Mishra

Journal Name: Current Drug Targets

Volume 22 , Issue 12 , 2021

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Graphical Abstract:


In neurodegenerative disorders, there is a progressive degeneration of the body, leading to the death of nerve cells. In this state, a patient gets affected day by day with mental weakness, dementia, and ataxia. Alzheimer’s disease (AD) is the most common irreversible neurodegenerative brain disorder mainly affecting people over the age of 65. Many types of research suggest that the main culprit for AD is the aggregated form of a (39-43) amino acid peptide called amyloid beta. Amyloid beta (Aβ) is generated by the action of beta-secretase and gamma-secretase on the larger glycoprotein. Gamma (γ) secretase is an intra-membrane protease complex that cleaves the single-- pass transmembrane protein, the amyloid precursor protein, and Notch. The γ-secretase complex contains presenilin, presenilin enhancer-2, anterior pharynx defective-1, and nicastrin. Any mutation in presenilin-1 or the cleavage of amyloid precursor protein by γ-secretase directly or indirectly is associated with AD. Therefore, the prevention of this enzyme is one of the solutions for AD. In this article, we discuss the γ-secretase complex and its inhibitors that can contribute to the prevention of AD.

Keywords: Neurodegenerative disorder, Alzheimer's disease, Amyloid beta, γ-secretase, Notch, presenilin, anterior pharynx defective-1, nicastrin, amyloid precursor protein.

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Article Details

Year: 2021
Published on: 30 December, 2020
Page: [1376 - 1403]
Pages: 28
DOI: 10.2174/1389450121999201230203709
Price: $65

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