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从实验研究到计算方法:淀粉样蛋白生成新型疗法设计的最新趋势

From experimental studies to computational approaches: recent trends in designing novel therapeutics for amyloidogenesis.

作者信息

Ghosh Pooja, Kundu Agnibin, Ganguly Debabani

机构信息

Centre for Interdisciplinary Sciences, JIS Institute of Advanced Studies & Research (JISIASR) Kolkata, JIS University, GP Block, Sector-5, Salt Lake, Kolkata 700091, West Bengal, India.

Department of Medicine, District Hospital Howrah, 10, Biplabi Haren Ghosh Sarani Lane, Howrah 711101, West Bengal, India.

出版信息

J Mater Chem B. 2025 Jan 15;13(3):858-881. doi: 10.1039/d4tb01890g.

DOI:10.1039/d4tb01890g
PMID:39664012
Abstract

Amyloidosis is a condition marked by misfolded proteins that build up in tissues and eventually destroy organs. It has been connected to a number of fatal illnesses, including non-neuropathic and neurodegenerative conditions, which in turn have a significant influence on the worldwide health sector. The inability to identify the underlying etiology of amyloidosis has hampered efforts to find a treatment for the condition. Despite the identification of a multitude of putative pathogenic variables that may operate independently or in combination, the molecular mechanisms responsible for the development and progression of the disease remain unclear. A thorough investigation into protein aggregation and the impacts of toxic aggregated species will help to clarify the cytotoxicity of aggregation-mediated cellular apoptosis and lay the groundwork for future studies aimed at creating effective treatments and medications. This review article provides a thorough summary of the combination of various experimental and computational approaches to modulate amyloid aggregation. Further, an overview of the latest developments of novel therapeutic agents is given, along with a discussion of the possible obstacles and viewpoints on this developing field. We believe that the information provided by this review will help scientists create innovative treatment strategies that affect the way proteins aggregate.

摘要

淀粉样变性是一种以错误折叠的蛋白质在组织中积聚并最终破坏器官为特征的病症。它与许多致命疾病有关,包括非神经病变性和神经退行性疾病,这些疾病进而对全球卫生部门产生重大影响。无法确定淀粉样变性的潜在病因阻碍了寻找该病症治疗方法的努力。尽管已经确定了许多可能单独或联合起作用的假定致病变量,但导致该疾病发生和发展的分子机制仍不清楚。对蛋白质聚集以及有毒聚集物的影响进行深入研究将有助于阐明聚集介导的细胞凋亡的细胞毒性,并为未来旨在开发有效治疗方法和药物的研究奠定基础。这篇综述文章全面总结了调节淀粉样蛋白聚集的各种实验和计算方法的结合。此外,还概述了新型治疗剂的最新进展,并讨论了这一发展领域可能存在的障碍和观点。我们相信,这篇综述提供的信息将有助于科学家制定影响蛋白质聚集方式的创新治疗策略。

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