Vahid Zahra Farajzadeh, Eskandani Morteza, Dadashi Hamed, Vandghanooni Somayeh, Rashidi Mohammad-Reza
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Heliyon. 2024 Nov 28;10(23):e40756. doi: 10.1016/j.heliyon.2024.e40756. eCollection 2024 Dec 15.
Alzheimer's disease (AD), a chronic neurodegenerative disease, is clinically characterized by loss of memory and learning ability among other neurological deficits. Amyloid plaques, hyperphosphorylated tau protein, and neurofibrillary tangles involve in AD etiology. Meanwhile, enzymes and their inhibitors have become the focus of research in AD treatment. In this review, the molecular mechanisms involved in the pathogenesis of AD were overviewed and various enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase, γ-secretase, monoamine oxidase (MAO), and receptor of advanced glycation end products (RAGE) were highlighted as potential targets for AD treatment. Several hybrid molecules with essential substructures derived from various chemotypes have demonstrated desired pharmacological activity. It is envisioned that the development of new drugs that inhibit enzymes involved in AD is a future trend in the management of the disease.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，其临床特征为记忆和学习能力丧失以及其他神经功能缺损。淀粉样斑块、过度磷酸化的tau蛋白和神经原纤维缠结参与了AD的病因学过程。同时，酶及其抑制剂已成为AD治疗研究的焦点。在本综述中，概述了AD发病机制中涉及的分子机制，并着重介绍了多种酶，如乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BuChE）、β-分泌酶、γ-分泌酶、单胺氧化酶（MAO）和晚期糖基化终末产物受体（RAGE），它们是AD治疗的潜在靶点。几种具有源自不同化学类型的必需亚结构的杂合分子已显示出理想的药理活性。可以预见，开发抑制参与AD的酶的新药是该疾病治疗的未来趋势。
