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合成聚合物对淀粉样蛋白纤维化的调控:神经退行性疾病背景下的最新进展

Modulation of Amyloid Protein Fibrillation by Synthetic Polymers: Recent Advances in the Context of Neurodegenerative Diseases.

作者信息

Ghosh Pooja, De Priyadarsi

机构信息

Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, 741246 Nadia, West Bengal, India.

出版信息

ACS Appl Bio Mater. 2020 Oct 19;3(10):6598-6625. doi: 10.1021/acsabm.0c01021. Epub 2020 Sep 21.

Abstract

Protein misfolding and aggregation have attracted immense research interests due to their connection with an array of degenerative diseases including neurodegenerative disorders and non-neuropathic diseases. Inhibition or diminution of the formation of protein aggregates is considered as a potential therapeutic strategy to cure these debilitating maladies. A large number of compounds including flavonoids, surfactants, osmolytes, vitamins, nanoparticles, etc. have been explored for impeding protein aggregation process and ameliorating neurodegenerative disorders. Even though a plethora of strategies have been designed to suppress protein aggregation, the final success rate is limited due to the lack of in-depth understanding of the aggregation pathway. In this context, polymeric materials are attracting the attention of researchers owing to their multifarious applications in the field of biomedical science and technology, and their unique properties as many parameters like functionality, molecular weight, architecture, etc. can be easily manipulated to improve their efficacy as well as meet clinical requirements. This review article highlights an outline of protein misfolding and aggregation, their mechanistic pathway, the factors responsible for aggregation, and potential therapeutic strategies for the intervention of those debilitating pathological conditions. Especially, the primary focus of this review article is to delineate the obligatory role of polymeric materials on protein aggregation pathway and encourage researchers to fabricate effective polymeric materials for designing next generation antiamyloidogenic therapeutic agents.

摘要

蛋白质错误折叠和聚集因其与一系列退行性疾病(包括神经退行性疾病和非神经病变性疾病)的关联而引发了广泛的研究兴趣。抑制或减少蛋白质聚集体的形成被视为治疗这些使人衰弱疾病的一种潜在治疗策略。人们已经探索了大量化合物,包括黄酮类化合物、表面活性剂、渗透剂、维生素、纳米颗粒等,以阻碍蛋白质聚集过程并改善神经退行性疾病。尽管已经设计了大量策略来抑制蛋白质聚集,但由于对聚集途径缺乏深入了解,最终成功率仍然有限。在这种背景下,高分子材料因其在生物医学科学与技术领域的多种应用以及其独特性质(如功能、分子量、结构等许多参数可以轻松操控以提高其功效并满足临床需求)而吸引了研究人员的关注。这篇综述文章重点介绍了蛋白质错误折叠和聚集的概述、其机制途径、聚集的相关因素以及干预这些使人衰弱的病理状况的潜在治疗策略。特别是,这篇综述文章的主要重点是阐述高分子材料在蛋白质聚集途径中的重要作用,并鼓励研究人员制造有效的高分子材料以设计下一代抗淀粉样生成治疗剂。

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