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微管稳定肽:治疗神经疾病的新范例

Microtubule stabilising peptides: new paradigm towards management of neuronal disorders.

作者信息

Bhargava Shubhangi, Kulkarni Riya, Dewangan Bhaskar, Kulkarni Neeraj, Jiaswar Chirag, Kumar Kunal, Kumar Amit, Bodhe Praveen Reddy, Kumar Hemant, Sahu Bichismita

机构信息

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Ahmedabad India

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Ahmedabad India.

出版信息

RSC Med Chem. 2023 Aug 14;14(11):2192-2205. doi: 10.1039/d3md00012e. eCollection 2023 Nov 15.

Abstract

Neuronal cells made of soma, axon, and dendrites are highly compartmentalized and possess a specialized transport system that can convey long-distance electrical signals for the cross-talk. The transport system is made up of microtubule (MT) polymers and MT-binding proteins. MTs play vital and diverse roles in various cellular processes. Therefore, defects and dysregulation of MTs and their binding proteins lead to many neurological disorders as exemplified by Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and many others. MT-stabilising agents (MSAs) altering the MT-associated protein connections have shown great potential for several neurodegenerative disorders. Peptides are an important class of molecules with high specificity, biocompatibility and are devoid of side effects. In the past, peptides have been explored in various neuronal disorders as therapeutics. Davunetide, a MT-stabilising octapeptide, has entered into phase II clinical trials for schizophrenia. Numerous examples of peptides emerging as MSAs reflect the emergence of a new paradigm for peptides which can be explored further as drug candidates for neuronal disorders. Although small molecule-based MSAs have been reviewed in the past, there is no systematic review in recent years focusing on peptides as MSAs apart from davunetide in 2013. Therefore, a systematic updated review on MT stabilising peptides may shed light on many hidden aspects and enable researchers to develop new therapies for diseases related to the CNS. In this review we have summarised the recent examples of peptides as MSAs.

摘要

由胞体、轴突和树突组成的神经元细胞高度分隔,并拥有一个专门的运输系统,该系统能够传递长距离电信号以进行细胞间通讯。该运输系统由微管(MT)聚合物和MT结合蛋白组成。MT在各种细胞过程中发挥着至关重要且多样的作用。因此,MT及其结合蛋白的缺陷和失调会导致许多神经系统疾病,如帕金森病、阿尔茨海默病、肌萎缩侧索硬化症、亨廷顿舞蹈症等等。改变MT相关蛋白连接的MT稳定剂(MSA)已在几种神经退行性疾病中显示出巨大潜力。肽是一类重要的分子,具有高特异性、生物相容性且无副作用。过去,肽已被探索用于各种神经元疾病的治疗。达武奈肽是一种MT稳定八肽,已进入精神分裂症的II期临床试验。众多作为MSA出现的肽的例子反映了一种新的肽范式的出现,这种肽可以作为神经元疾病的候选药物进一步探索。尽管过去已经对基于小分子的MSA进行了综述,但近年来除了2013年的达武奈肽外,没有针对作为MSA的肽的系统综述。因此,对MT稳定肽进行系统的更新综述可能会揭示许多隐藏的方面,并使研究人员能够开发针对中枢神经系统相关疾病的新疗法。在本综述中,我们总结了最近作为MSA的肽的例子。

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