Department of Biopharmacy, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
Int J Mol Sci. 2022 May 29;23(11):6085. doi: 10.3390/ijms23116085.
Alzheimer's disease (AD) is multifactorial, progressive and the most predominant cause of cognitive impairment and dementia worldwide. The current "one-drug, one-target" approach provides only symptomatic relief to the condition but is unable to cure the disease completely. The conventional single-target therapeutic approach might not always induce the desired effect due to the multifactorial nature of AD. Hence, multitarget strategies have been proposed to simultaneously knock out multiple targets involved in the development of AD. Herein, we provide an overview of the various strategies, followed by the multitarget-directed ligand (MTDL) development, rationale designs and efficient examples. Furthermore, the effects of the linkers and substitutional functional groups on MTDLs against various targets of AD and their modes of action are also discussed.
阿尔茨海默病（AD）是一种多因素、进行性疾病，也是全球认知障碍和痴呆的主要原因。目前的“一种药物，一个靶点”的方法只能为这种疾病提供对症缓解，而不能完全治愈这种疾病。由于 AD 的多因素性质，传统的单一靶点治疗方法可能并不总是能产生预期的效果。因此，已经提出了多靶点策略来同时敲除 AD 发展过程中涉及的多个靶点。本文首先概述了各种策略，然后介绍了多靶点配体（MTDL）的开发、合理设计和有效实例。此外，还讨论了连接子和取代功能性基团对 MTDL 针对 AD 各种靶点的影响及其作用模式。
