Assembly of Aβ Proceeds via Monomeric Nuclei

Frank A. Ferrone

doi:10.1016/j.jmb.2014.10.028

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Assembly of Aβ Proceeds via Monomeric Nuclei

Journal article

Peer reviewed

Assembly of Aβ Proceeds via Monomeric Nuclei

Frank A. Ferrone

Journal of molecular biology, v 427(2), pp 287-290

30 Jan 2015

DOI: https://doi.org/10.1016/j.jmb.2014.10.028

PMID: 25451026

Featured in Collection : UN Sustainable Development Goals @ Drexel

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Abstract

Alzheimer's disease

lag time

nucleation

polymerization

protein folding

Aggregation of amyloid-β (Aβ) peptides is fundamental to Alzheimer's disease. It has now been shown that nucleated proliferation of Aβ fibrils utilizes a secondary mechanism with existing fibrils catalyzing the formation of new ones. Here it is shown that the data for Aβ40 and Aβ42 require that the nuclei be monomeric; that is, an initial, unfavorable conformational change is rate limiting for the processes that appear to be nucleation. Following the conformational change, the assembly process is “downhill” despite clear lag times and significant concentration dependence. The similarity to polyglutamine nucleation suggests that monomeric nuclei may be widespread in amyloid formation. [Display omitted] •Aβ fibril formation kinetics require monomeric nuclei.•This is true for primary and secondary nucleation.•This means that, once conformational change occurs, growth is a downhill process.•Similarities with polyglutamine assembly suggest that this may be widespread.