{"title":"了解和克服AL淀粉样变性的生化多样性","authors":"Gareth J. Morgan","doi":"10.1002/ijch.202300128","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"15 3","pages":"0"},"PeriodicalIF":2.3000,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Understanding and Overcoming Biochemical Diversity in AL Amyloidosis\",\"authors\":\"Gareth J. Morgan\",\"doi\":\"10.1002/ijch.202300128\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":14686,\"journal\":{\"name\":\"Israel Journal of Chemistry\",\"volume\":\"15 3\",\"pages\":\"0\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-11-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Israel Journal of Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/ijch.202300128\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Israel Journal of Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/ijch.202300128","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
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.
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.