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阿尔茨海默病的发病机制、动物模型和药物发现。

Pathogenesis, Animal Models, and Drug Discovery of Alzheimer's Disease.

机构信息

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, PR China.

Department of Pharmacy, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, PR China.

出版信息

J Alzheimers Dis. 2023;94(4):1265-1301. doi: 10.3233/JAD-230326.

DOI:10.3233/JAD-230326
PMID:37424469
Abstract

Alzheimer's disease (AD), the most common cause of dementia, is a chronic neurodegenerative disease induced by multiple factors. The high incidence and the aging of the global population make it a growing global health concern with huge implications for individuals and society. The clinical manifestations are progressive cognitive dysfunction and lack of behavioral ability, which not only seriously affect the health and quality of life of the elderly, but also bring a heavy burden to the family and society. Unfortunately, almost all the drugs targeting the classical pathogenesis have not achieved satisfactory clinical effects in the past two decades. Therefore, the present review provides more novel ideas on the complex pathophysiological mechanisms of AD, including classical pathogenesis and a variety of possible pathogenesis that have been proposed in recent years. It will be helpful to find out the key target and the effect pathway of potential drugs and mechanisms for the prevention and treatment of AD. In addition, the common animal models in AD research are outlined and we examine their prospect for the future. Finally, Phase I, II, III, and IV randomized clinical trials or on the market of drugs for AD treatment were searched in online databases (Drug Bank Online 5.0, the U.S. National Library of Medicine, and Alzforum). Therefore, this review may also provide useful information in the research and development of new AD-based drugs.

摘要

阿尔茨海默病(AD)是最常见的痴呆症病因,是一种由多种因素引起的慢性神经退行性疾病。其高发病率和全球人口老龄化使其成为一个日益严重的全球健康问题,对个人和社会都有重大影响。其临床症状为进行性认知功能障碍和行为能力丧失,不仅严重影响老年人的健康和生活质量,也给家庭和社会带来沉重负担。不幸的是,在过去的二十年中,几乎所有针对经典发病机制的药物都没有取得令人满意的临床效果。因此,本综述为 AD 复杂病理生理机制提供了更多新颖的思路,包括经典发病机制和近年来提出的多种可能发病机制。这将有助于发现 AD 潜在药物的关键靶点和作用途径及其预防和治疗的机制。此外,还概述了 AD 研究中常见的动物模型,并对其未来进行了考察。最后,在在线数据库(Drug Bank Online 5.0、美国国家医学图书馆和 Alzforum)中搜索了 AD 治疗药物的 I、II、III 和 IV 期随机临床试验或已上市药物。因此,本综述在 AD 相关新药的研发中也可能提供有用的信息。

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