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TitleDistribution of Amyloid-Like and Oligomeric Species from Protein Aggregation Kinetics
Author(s)Silva, Alexandra
Almeida, Bruno
Fraga, Joana S.
Taboada, Pablo
Martins, Pedro M.
Macedo-Ribeiro, Sandra
Chromatography, Gel
Microscopy, Electron, Transmission
Protein Binding
Repressor Proteins
protein aggregation
soluble oligomers
Issue date2017
PublisherJohn Wiley & Sons
JournalAngewandte Chemie - International Edition
CitationSilva, 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
Abstract(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.
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AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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