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阿尔茨海默病治疗的分子机制、靶点和新型分子。

The molecular mechanism, targets, and novel molecules in the treatment of Alzheimer's disease.

机构信息

Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.

Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.

出版信息

Bioorg Chem. 2022 Feb;119:105562. doi: 10.1016/j.bioorg.2021.105562. Epub 2021 Dec 16.

Abstract

Alzheimer's disease (AD) is a progressive neurological illness that causes dementia mainly in the elderly. The challenging obstacles related to AD has freaked global healthcare system to encourage scientists in developing novel therapeutic startegies to overcome with the fatal disease. The current treatment therapy of AD provides only symptomatic relief and to some extent disease-modifying effects. The current approach for AD treatment involves designing of cholinergic inhibitors, Aβ disaggregation inducing agents, tau inhibitors and several antioxidants. Hence, extensive research on AD therapy urgently requires a deep understanding of its pathophysiology and exploration of various chemical scaffolds to design and develop a potential drug candidate for the treatment. Various issues linked between disease and therapy need to be considered such as BBB penetration capability, clinical failure and multifaceted pathophisiology requires a proper attention to develop a lead candidate. This review article covers all probable mechanisms including one of the recent areas for investigation i.e., lipid dyshomeostasis, pathogenic involvement of P. gingivalis and neurovascular dysfunction, recently reported molecules and drugs under clinical investigations and approved by FDA for AD treatment. Our summarized information on AD will attract the researchers to understand and explore current status and structural modifications of the recently reported heterocyclic derivatives in drug development for AD therapy.

摘要

阿尔茨海默病(AD)是一种进行性神经疾病,主要发生在老年人中导致痴呆。与 AD 相关的具有挑战性的障碍使全球医疗保健系统感到恐惧,鼓励科学家开发新的治疗策略来克服这种致命疾病。目前 AD 的治疗方法仅提供症状缓解,在一定程度上具有疾病修饰作用。目前 AD 治疗的方法包括设计胆碱能抑制剂、Aβ解聚诱导剂、tau 抑制剂和几种抗氧化剂。因此,AD 治疗的广泛研究迫切需要深入了解其病理生理学,并探索各种化学支架,以设计和开发治疗的潜在药物候选物。需要考虑与疾病和治疗相关的各种问题,如 BBB 穿透能力、临床失败和多方面的病理生理学,需要适当关注以开发出先导候选物。本文综述了包括最近研究领域之一的所有可能机制,即脂代谢失衡、P. gingivalis 的致病作用和神经血管功能障碍,最近报道的分子和药物正在进行临床试验,并获得了 FDA 批准用于 AD 治疗。我们对 AD 的总结信息将吸引研究人员了解和探索最近报道的杂环衍生物在 AD 治疗药物开发中的现状和结构修饰。

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