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治疗阿尔茨海默病的多靶药物。

Multi-target drugs for Alzheimer's disease.

机构信息

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, Columbia University, 650 West 168th Street, New York, NY 10032, USA; Department of Neurology, Columbia University Irving Medical Center, Columbia University, 710 West 168th Street, New York, NY 10032, USA.

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, Columbia University, 650 West 168th Street, New York, NY 10032, USA; Department of Neurology, Columbia University Irving Medical Center, Columbia University, 710 West 168th Street, New York, NY 10032, USA; Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University Irving Medical Center, Columbia University, 630 West 168th Street, New York, NY, USA.

出版信息

Trends Pharmacol Sci. 2024 Jul;45(7):628-638. doi: 10.1016/j.tips.2024.05.005. Epub 2024 Jun 9.

Abstract

Alzheimer's disease (AD), a leading cause of dementia, increasingly challenges our healthcare systems and society. Traditional therapies aimed at single targets have fallen short owing to the complex, multifactorial nature of AD that necessitates simultaneous targeting of various disease mechanisms for clinical success. Therefore, targeting multiple pathologies at the same time could provide a synergistic therapeutic effect. The identification of new disease targets beyond the classical hallmarks of AD offers a fertile ground for the design of new multi-target drugs (MTDs), and building on existing compounds have the potential to yield in successful disease modifying therapies. This review discusses the evolving landscape of MTDs, focusing on their potential as AD therapeutics. Analysis of past and current trials of compounds with multi-target activity underscores the capacity of MTDs to offer synergistic therapeutic effects, and the flourishing genetic understanding of AD will inform and inspire the development of MTD-based AD therapies.

摘要

阿尔茨海默病(AD)是痴呆症的主要病因,它日益给我们的医疗保健系统和社会带来挑战。由于 AD 的复杂性和多因素性质,传统的针对单一靶点的治疗方法已经失败,因为需要同时针对各种疾病机制才能取得临床成功。因此,同时针对多种病变可能会产生协同的治疗效果。除了 AD 的经典标志之外,确定新的疾病靶点为设计新的多靶药物(MTD)提供了肥沃的土壤,并且利用现有化合物有可能产生成功的疾病修饰治疗方法。本综述讨论了 MTD 的不断发展的前景,重点关注它们作为 AD 治疗药物的潜力。对具有多靶活性的化合物的过去和当前试验的分析强调了 MTD 提供协同治疗效果的能力,而对 AD 的日益深入的遗传理解将为基于 MTD 的 AD 治疗方法的开发提供信息和启发。

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