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阿尔茨海默病新型药物研发中多靶点的综合研究

Comprehensive investigation of multiple targets in the development of newer drugs for the Alzheimer's disease.

作者信息

Ashwini Patil, Subhash Bodhankar, Amol Muthal, Kumar Dileep, Atmaram Pawar, Ravindra Kulkarni

机构信息

Department of Pharmaceutical Chemistry, BVDU'S Poona College of Pharmacy, Erandwane Pune-411038, Maharashtra, India.

Department of Pharmacology, BVDU'S Poona College of Pharmacy, Erandwane Pune-411038, Maharashtra, India.

出版信息

Acta Pharm Sin B. 2025 Mar;15(3):1281-1310. doi: 10.1016/j.apsb.2024.11.016. Epub 2024 Nov 26.

DOI:10.1016/j.apsb.2024.11.016
PMID:40370532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12069117/
Abstract

Alzheimer's disease, a significant contributor to dementia, is rapidly becoming a serious healthcare concern in the 21st century. The alarming number of patients with Alzheimer's disease is steadily increasing, which is contributed by the dearth of treatment options. The current treatment for Alzheimer's disease is heavily dependent on symptomatic treatment that has failed to cure the disease despite huge investments in the development of drugs. The clinical treatment of Alzheimer's disease with limited drugs is generally targeted towards the inhibition of -methyl-d-aspartate receptor and acetylcholine esterase, which only elevate cognition levels for a limited period. Beyond the aforementioned molecular targets, -amyloid was much explored with little success and thus created a feel and palpable growing emphasis on discovering new putative and novel targets for AD. This has inspired medicinal chemists to explore new targets, including microglia, triggering receptors expressed on myeloid cells 2 (Trem-2), and notum carboxylesterase, to discover new lead compounds. This review explores the functions, pathophysiological roles, and importance of all AD-related targets that address therapeutic and preventive approaches for the treatment and protection of Alzheimer's disease.

摘要

阿尔茨海默病是痴呆症的一个重要成因，在21世纪正迅速成为一个严重的医疗保健问题。阿尔茨海默病患者数量惊人且在稳步增加，这是由于治疗方案匮乏所致。目前针对阿尔茨海默病的治疗严重依赖对症治疗，尽管在药物研发上投入巨大，但仍未能治愈该疾病。使用有限药物对阿尔茨海默病进行临床治疗通常旨在抑制N-甲基-D-天冬氨酸受体和乙酰胆碱酯酶，而这仅能在有限时间内提高认知水平。除了上述分子靶点外，对β-淀粉样蛋白进行了大量研究但收效甚微，因此人们越来越强烈地感到需要发现针对阿尔茨海默病的新的假定靶点。这激励药物化学家探索新的靶点，包括小胶质细胞、髓系细胞触发受体2（Trem-2）和Notum羧酸酯酶，以发现新的先导化合物。本综述探讨了所有与阿尔茨海默病相关靶点的功能、病理生理作用及其重要性，这些靶点涉及治疗和预防阿尔茨海默病的方法。

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