Haldia Institute of Pharmacy, Kshudiram Nagar, Haldia-721657, West Bengal, India.
Pirijpur-Rankini mahula, Jamalpur, Purba Burdwan-713404, West Bengal, India.
Curr Drug Targets. 2021;22(12):1376-1403. doi: 10.2174/1389450121999201230203709.
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.
在神经退行性疾病中，身体会逐渐退化，导致神经细胞死亡。在这种状态下，患者会一天天受到精神衰弱、痴呆和共济失调的影响。阿尔茨海默病（AD）是最常见的不可逆神经退行性脑疾病，主要影响 65 岁以上的人群。许多类型的研究表明，AD 的主要罪魁祸首是一种（39-43）氨基酸肽的聚集形式，称为淀粉样β。淀粉样β（Aβ）是由β-分泌酶和γ-分泌酶对较大糖蛋白的作用产生的。γ（γ）分泌酶是一种跨膜蛋白酶复合物，可切割单次跨膜蛋白、淀粉样前体蛋白和 Notch。γ-分泌酶复合物包含早老素-1、早老素增强子-2、前咽缺陷蛋白-1 和 Nicastrin。早老素-1 中的任何突变或 γ-分泌酶对淀粉样前体蛋白的切割直接或间接地与 AD 有关。因此，预防这种酶是 AD 的解决方案之一。本文讨论了γ-分泌酶复合物及其抑制剂，它们可以有助于预防 AD。
