Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/62022

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
KeywordsAmyloid
Ataxin-3
Biopolymers
Chromatography, Gel
Kinetics
Microscopy, Electron, Transmission
Protein Binding
Proteins
Repressor Proteins
protein aggregation
self-assembly
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.
TypeArticle
URIhttp://hdl.handle.net/1822/62022
DOI10.1002/anie.201707345
ISSN1433-7851
e-ISSN1521-3773
Publisher versionhttps://onlinelibrary.wiley.com/doi/full/10.1002/anie.201707345
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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