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杂环化合物在神经退行性疾病中的治疗作用:来自阿尔茨海默病和帕金森病的见解

Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer's and Parkinson's Diseases.

作者信息

Puranik Nidhi, Song Minseok

机构信息

Department of Life Sciences, Yeungnam University, Gyeongsan 38541, Republic of Korea.

出版信息

Neurol Int. 2025 Feb 7;17(2):26. doi: 10.3390/neurolint17020026.

Abstract

Alzheimer's and Parkinson's are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates and the progressive and permanent loss of neurons are the major characteristic features of these disorders. Although the precise mechanisms causing Alzheimer's disease (AD) and Parkinson's disease (PD) are still unknown, there is a wealth of evidence suggesting that misfolded proteins, accumulation of misfolded proteins, dysfunction of neuroreceptors and mitochondria, dysregulation of enzymes, and the release of neurotransmitters significantly influence the pathophysiology of these diseases. There is no effective protective medicine or therapy available even with the availability of numerous medications. There is an urgent need to create new and powerful bioactive compounds since the number of people with NDDs is rising globally. Heterocyclic compounds have consistently played a pivotal role in drug discovery due to their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine hydrochloride, and opicapone, feature heterocyclic cores. As these heterocyclic compounds have exceptional therapeutic potential, heterocycles are an intriguing research topic for the development of new effective therapeutic drugs for PD and AD. This review aims to provide current insights into the development and potential use of heterocyclic compounds targeting diverse therapeutic targets to manage and potentially treat patients with AD and PD.

摘要

阿尔茨海默病和帕金森病是最常见的神经退行性疾病。异常蛋白质聚集体的形成以及神经元的进行性和永久性丧失是这些疾病的主要特征。尽管导致阿尔茨海默病(AD)和帕金森病(PD)的确切机制仍不清楚,但有大量证据表明,错误折叠的蛋白质、错误折叠蛋白质的积累、神经受体和线粒体功能障碍、酶的失调以及神经递质的释放会显著影响这些疾病的病理生理学。即使有大量药物可用,也没有有效的预防药物或疗法。由于全球神经退行性疾病患者数量不断增加,迫切需要开发新的强效生物活性化合物。杂环化合物因其卓越的药学性质,在药物发现中一直发挥着关键作用。许多临床批准的药物,如氢溴酸加兰他敏、盐酸多奈哌齐、盐酸美金刚和奥匹卡朋,都具有杂环核心。由于这些杂环化合物具有卓越的治疗潜力,杂环是开发用于治疗帕金森病和阿尔茨海默病的新型有效治疗药物的一个有趣研究课题。本综述旨在提供有关靶向不同治疗靶点的杂环化合物的开发及其潜在用途的最新见解,以管理并潜在治疗阿尔茨海默病和帕金森病患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb7/11858632/d327bb4e3ef9/neurolint-17-00026-g001.jpg

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