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

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.