Siddhartha Banerjee, Divya Baghel, Harrison O. Edmonds, Ayanjeet Ghosh
{"title":"异型播种产生混合淀粉样蛋白多态性","authors":"Siddhartha Banerjee, Divya Baghel, Harrison O. Edmonds, Ayanjeet Ghosh","doi":"10.1002/smsc.202400109","DOIUrl":null,"url":null,"abstract":"Aggregation of the amyloid β (Aβ) peptide into fibrils represents one of the major biochemical pathways underlying the development of Alzheimer's disease (AD). Extensive studies have been carried out to understand the role of fibrillar seeds on the overall kinetics of amyloid aggregation. However, the precise effect of seeds that are structurally or sequentially different from Aβ on the structure of the resulting amyloid aggregates is yet to be fully understood. Herein, nanoscale infrared spectroscopy is used to probe the spectral facets of individual aggregates formed by aggregating Aβ42 with antiparallel fibrillar seeds of Aβ(16–22) and E22Q Aβ(1–40) Dutch mutant and it is demonstrated that Aβ can form heterotypic or mixed polymorphs that deviate significantly from its expected parallel cross β structure. It is further shown that the formation of heterotypic aggregates is not limited to the coaggregation of Aβ and its isomers, and that the former can form heterotypic fibrils with alpha-synuclein and brain protein lysates. These findings highlight the complexity of Aβ aggregation in AD and underscore the need to explore how Aβ interacts with other brain components, which is crucial for developing better therapeutic strategies for AD.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"145 1","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Heterotypic Seeding Generates Mixed Amyloid Polymorphs\",\"authors\":\"Siddhartha Banerjee, Divya Baghel, Harrison O. Edmonds, Ayanjeet Ghosh\",\"doi\":\"10.1002/smsc.202400109\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Aggregation of the amyloid β (Aβ) peptide into fibrils represents one of the major biochemical pathways underlying the development of Alzheimer's disease (AD). Extensive studies have been carried out to understand the role of fibrillar seeds on the overall kinetics of amyloid aggregation. However, the precise effect of seeds that are structurally or sequentially different from Aβ on the structure of the resulting amyloid aggregates is yet to be fully understood. Herein, nanoscale infrared spectroscopy is used to probe the spectral facets of individual aggregates formed by aggregating Aβ42 with antiparallel fibrillar seeds of Aβ(16–22) and E22Q Aβ(1–40) Dutch mutant and it is demonstrated that Aβ can form heterotypic or mixed polymorphs that deviate significantly from its expected parallel cross β structure. It is further shown that the formation of heterotypic aggregates is not limited to the coaggregation of Aβ and its isomers, and that the former can form heterotypic fibrils with alpha-synuclein and brain protein lysates. These findings highlight the complexity of Aβ aggregation in AD and underscore the need to explore how Aβ interacts with other brain components, which is crucial for developing better therapeutic strategies for AD.\",\"PeriodicalId\":29791,\"journal\":{\"name\":\"Small Science\",\"volume\":\"145 1\",\"pages\":\"\"},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2024-06-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Small Science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/smsc.202400109\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Small Science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/smsc.202400109","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Aggregation of the amyloid β (Aβ) peptide into fibrils represents one of the major biochemical pathways underlying the development of Alzheimer's disease (AD). Extensive studies have been carried out to understand the role of fibrillar seeds on the overall kinetics of amyloid aggregation. However, the precise effect of seeds that are structurally or sequentially different from Aβ on the structure of the resulting amyloid aggregates is yet to be fully understood. Herein, nanoscale infrared spectroscopy is used to probe the spectral facets of individual aggregates formed by aggregating Aβ42 with antiparallel fibrillar seeds of Aβ(16–22) and E22Q Aβ(1–40) Dutch mutant and it is demonstrated that Aβ can form heterotypic or mixed polymorphs that deviate significantly from its expected parallel cross β structure. It is further shown that the formation of heterotypic aggregates is not limited to the coaggregation of Aβ and its isomers, and that the former can form heterotypic fibrils with alpha-synuclein and brain protein lysates. These findings highlight the complexity of Aβ aggregation in AD and underscore the need to explore how Aβ interacts with other brain components, which is crucial for developing better therapeutic strategies for AD.
期刊介绍:
Small Science is a premium multidisciplinary open access journal dedicated to publishing impactful research from all areas of nanoscience and nanotechnology. It features interdisciplinary original research and focused review articles on relevant topics. The journal covers design, characterization, mechanism, technology, and application of micro-/nanoscale structures and systems in various fields including physics, chemistry, materials science, engineering, environmental science, life science, biology, and medicine. It welcomes innovative interdisciplinary research and its readership includes professionals from academia and industry in fields such as chemistry, physics, materials science, biology, engineering, and environmental and analytical science. Small Science is indexed and abstracted in CAS, DOAJ, Clarivate Analytics, ProQuest Central, Publicly Available Content Database, Science Database, SCOPUS, and Web of Science.