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dc.contributor.authorMorel, Bertrand
dc.contributor.authorCarrasco Jiménez, María Paz 
dc.contributor.authorJurado, Samuel
dc.contributor.authorConejero Lara, Francisco
dc.identifier.citationMorel, B.; Carrasco-Jiménez, M.P.; Jurado, S.; Conejero-Lara, F. Rapid Conversion of Amyloid-Beta 1-40 Oligomers to Mature Fibrils through a Self-Catalytic Bimolecular Process. Int. J. Mol. Sci. 2021, 22, 6370. ijms22126370es_ES
dc.description.abstractThe formation of fibrillar aggregates of the amyloid beta peptide (Aβ) in the brain is one of the hallmarks of Alzheimer’s disease (AD). A clear understanding of the different aggregation steps leading to fibrils formation is a keystone in therapeutics discovery. In a recent study, we showed that Aβ40 and Aβ42 form dynamic micellar aggregates above certain critical concentrations, which mediate a fast formation of more stable oligomers, which in the case of Aβ40 are able to evolve towards amyloid fibrils. Here, using different biophysical techniques we investigated the role of different fractions of the Aβ aggregation mixture in the nucleation and fibrillation steps. We show that both processes occur through bimolecular interplay between low molecular weight species (monomer and/or dimer) and larger oligomers. Moreover, we report here a novel self-catalytic mechanism of fibrillation of Aβ40, in which early oligomers generate and deliver low molecular weight amyloid nuclei, which then catalyze the rapid conversion of the oligomers to mature amyloid fibrils. This fibrillation catalytic activity is not present in freshly disaggregated low-molecular weight Aβ40 and is, therefore, a property acquired during the aggregation process. In contrast to Aβ40, we did not observe the same self-catalytic fibrillation in Aβ42 spheroidal oligomers, which could neither be induced to fibrillate by the Aβ40 nuclei. Our results reveal clearly that amyloid fibrillation is a multi-component process, in which dynamic collisions between different interacting species favor the kinetics of amyloid nucleation and growth.es_ES
dc.description.sponsorshipSpanish Ministry of Economy and Competitivity (BIO2013-40697-R) (BIO2016-76640-R) - European Regional Development Fund of the European Union.es_ES
dc.rightsAtribución 3.0 España*
dc.subjectAggregation kineticses_ES
dc.subjectCatalysis es_ES
dc.titleRapid Conversion of Amyloid-Beta 1-40 Oligomers to Mature Fibrils through a Self-Catalytic Bimolecular Processes_ES

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Atribución 3.0 España
Except where otherwise noted, this item's license is described as Atribución 3.0 España