了解和克服AL淀粉样变性的生化多样性

IF 2.3 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Gareth J. Morgan
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引用次数: 0

摘要

淀粉样蛋白原纤维沉积在全身性淀粉样蛋白疾病中可导致进行性组织损伤和器官衰竭,抑制其聚集的治疗可带来临床益处。通过结合前体蛋白来阻止聚集的小分子对淀粉样转甲状腺素(ATTR)淀粉样变性有效。然而,在淀粉样蛋白轻链(AL)淀粉样变性中,原纤维是由抗体轻链形成的,每个患者都有独特的蛋白质序列聚集。这些轻链的高度多样化的序列似乎决定了一个人是否有淀粉样变的风险,淀粉样蛋白沉积的分布和疾病的进展。因此,轻链是具有挑战性的药物靶点。本综述探讨了AL淀粉样变性和ATTR淀粉样变性之间的相似之处,以描述可以稳定轻链的小分子的发现。这些分子有可能作为AL淀粉样变性的治疗方法,突出了在其他蛋白质错误折叠疾病中发现药物的潜在机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Understanding and Overcoming Biochemical Diversity in AL Amyloidosis

Understanding and Overcoming Biochemical Diversity in AL Amyloidosis
Abstract Amyloid fibril deposition causes progressive tissue damage and organ failure in the systemic amyloid diseases, and therapies that suppress aggregation lead to clinical benefit. Small molecules that prevent aggregation by binding to precursor proteins are effective for amyloid transthyretin (ATTR) amyloidosis. However, in amyloid light chain (AL) amyloidosis, fibrils are formed by antibody light chains and every patient has a unique protein sequence that aggregates. The highly diverse sequences of these light chains appear to determine whether an individual is at risk of amyloidosis, the distribution of amyloid deposits and the progression of disease. Light chains are therefore challenging drug targets. This review explores the parallels between AL amyloidosis and ATTR amyloidosis to describe the discovery of small molecules that can stabilize light chains. These molecules have potential as therapies for AL amyloidosis, highlighting potential opportunities for drug discovery in other diseases of protein misfolding.
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来源期刊
Israel Journal of Chemistry
Israel Journal of Chemistry 化学-化学综合
CiteScore
6.20
自引率
0.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The fledgling State of Israel began to publish its scientific activity in 1951 under the general heading of Bulletin of the Research Council of Israel, which quickly split into sections to accommodate various fields in the growing academic community. In 1963, the Bulletin ceased publication and independent journals were born, with Section A becoming the new Israel Journal of Chemistry. The Israel Journal of Chemistry is the official journal of the Israel Chemical Society. Effective from Volume 50 (2010) it is published by Wiley-VCH. The Israel Journal of Chemistry is an international and peer-reviewed publication forum for Special Issues on timely research topics in all fields of chemistry: from biochemistry through organic and inorganic chemistry to polymer, physical and theoretical chemistry, including all interdisciplinary topics. Each topical issue is edited by one or several Guest Editors and primarily contains invited Review articles. Communications and Full Papers may be published occasionally, if they fit with the quality standards of the journal. The publication language is English and the journal is published twelve times a year.
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