Departmental Section of Physiology. Faculty of Pharmacy. Universidad Complutense de Madrid. Madrid 28040, Spain ; Biotransformations Group, Universidad Complutense de Madrid 28040, Spain.
Department of Organic and Pharmaceutical Chemistry. Faculty of Pharmacy. Universidad Complutense de Madrid 28040, Spain.
Curr Neuropharmacol. 2014 Jan;12(1):2-36. doi: 10.2174/1570159X113116660047.
The lack of an adequate therapy for Alzheimer's Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm "Multi-Target-Directed Ligands" (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches.
阿尔茨海默病(AD)缺乏有效的治疗方法在很大程度上导致了相关文献和综述数量的不断增加,这反映了该领域科学家所做的重要努力。众所周知,AD 是痴呆症最常见的原因,而目前尚无预防疗法,也无法治愈该疾病,这与科学家们为此付出的巨大努力形成鲜明对比。另一方面,AD 的许多方面目前仍存在争议,甚至有些方面还不为人知。本综述介绍了 AD 的最新研究进展,包括与疾病相关的更相关的发现和过程;同时还考虑了新的“多靶点定向配体”(MTDLs)范式,介绍了更多关于治疗药物的过去、现在和未来的研究。我们认为,从现在起,这一范式将引领研究人员发现更好的治疗方法,不仅在 AD 领域,而且在其他复杂疾病领域也是如此。本文综述了目前的研究策略,并重点介绍了其他新兴的靶点,这些靶点应在未来新的 MTDLs 开发中得到考虑。因此,本综述的研究路径从 AD 的病理学和涉及的过程开始,最终聚焦于目前和未来研究中需要考虑的策略。