Neurodegenerative diseases represent nowadays one of the major health problems. Despite the efforts made to unveil the mechanism leading to neurodegeneration, it is still not entirely clear what triggers this phenomenon and what allows its progression. Nevertheless, it is accepted that neurodegeneration is a consequence of several detrimental processes, such as protein aggregation, oxidative stress, and neuroinflammation, finally resulting in the loss of neuronal functions. Starting from these evidences, there has been a wide search for novel agents able to address more than a single event at the same time, the so-called multitarget-directed ligands (MTDLs). These compounds originated from the combination of different pharmacophoric elements which endowed them with the ability to interfere with different enzymatic and/or receptor systems, or to exert neuroprotective effects by modulating proteins and metal homeostasis. MTDLs have been the focus of the latest strategies to discover a new treatment for Alzheimer’s disease (AD), which is considered the most common form of dementia characterized by neurodegeneration and cognitive dysfunctions. This review is aimed at collecting the latest and most interesting target combinations for the treatment of AD, with a detailed discussion on new agents with favorable in vitro properties and on optimized structures that have already been assessed in vivo in animal models of dementia.

中文翻译：

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阿尔茨海默氏病的多靶点治疗策略：新兴靶点组合的综述。

如今，神经退行性疾病是主要的健康问题之一。尽管为揭示导致神经退行性变的机制做出了努力，但仍不清楚是什么触发了这种现象以及什么导致了这种现象的发展。然而，人们公认神经变性是几种有害过程的结果，例如蛋白质聚集，氧化应激和神经炎症，最终导致神经元功能丧失。从这些证据出发，人们在寻找能够同时解决多个事件的新型药物，即所谓的多靶标配体（MTDL）。这些化合物源自不同药效学元素的组合，赋予它们干扰不同酶和/或受体系统的能力，或通过调节蛋白质和金属稳态来发挥神经保护作用。MTDL一直是发现新疗法以治疗阿尔茨海默氏病（AD）的最新策略的重点，AD被认为是以神经变性和认知功能障碍为特征的最常见的痴呆形式。这篇综述旨在收集用于治疗AD的最新和最有趣的靶点组合，并详细讨论对治疗AD有益的新药。痴呆动物模型已在体内评估了体外特性和优化结构。