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https://hdl.handle.net/1822/62022
Título: | Distribution of Amyloid-Like and Oligomeric Species from Protein Aggregation Kinetics |
Autor(es): | Silva, Alexandra Almeida, Bruno Fraga, Joana S. Taboada, Pablo Martins, Pedro Manuel Abreu Macedo-Ribeiro, Sandra |
Palavras-chave: | Amyloid Ataxin-3 Biopolymers Chromatography, Gel Kinetics Microscopy, Electron, Transmission Protein Binding Proteins Repressor Proteins protein aggregation self-assembly soluble oligomers |
Data: | 2017 |
Editora: | John Wiley & Sons |
Revista: | Angewandte Chemie - International Edition |
Citação: | Silva, A., Almeida, B., et. al.(2017). Distribution of Amyloid‐Like and Oligomeric Species from Protein Aggregation Kinetics. Angewandte Chemie International Edition, 56(45), 14042-14045 |
Resumo(s): | Amyloid fibrils and soluble oligomers are two types of protein aggregates associated with neurodegeneration. Classic therapeutic strategies try to prevent the nucleation and spread of amyloid fibrils, whilst diffusible oligomers have emerged as promising drug targets affecting downstream pathogenic processes. We developed a generic protein aggregation model and validate it against measured compositions of fibrillar and non-fibrillar assemblies of ataxin-3, a protein implicated in Machado-Joseph disease. The derived analytic rate-law equations can be used to 1) identify the presence of parallel aggregation pathways and 2) estimate the critical sizes of amyloid fibrils. The discretized population balance supporting our model is the first to quantitatively fit time-resolved measurements of size and composition of both amyloid-like and oligomeric species. The new theoretical framework can be used to screen a new class of drugs specifically targeting toxic oligomers. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/62022 |
DOI: | 10.1002/anie.201707345 |
ISSN: | 1433-7851 |
e-ISSN: | 1521-3773 |
Versão da editora: | https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201707345 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Silva-2017-Distribution-of-amyloid-like-and-ol.pdf Acesso restrito! | 2,52 MB | Adobe PDF | Ver/Abrir |