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Research article - Peer-reviewed, 2012

Hydrophobicity and Conformational Change as Mechanistic Determinants for Nonspecific Modulators of Amyloid beta Self-Assembly

Abelein, Axel; Bolognesi, Benedetta; Dobson, Christopher M.; Graslund, Astrid; Lendel, Christofer


The link between many neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, and the aberrant folding and aggregation of proteins has prompted a comprehensive search for small organic molecules that have the potential to inhibit such processes. Although many compounds have been reported to affect the formation of amyloid fibrils and/or other types of protein aggregates, the mechanisms by which they act are not well understood. A large number of compounds appear to act in a nonspecific way affecting several different amyloidogenic proteins. We describe here a detailed study of the mechanism of action of one representative compound, lacmoid, in the context of the inhibition of the aggregation of the amyloid beta-peptide (A beta) associated with Alzheimer's disease. We show that lacmoid binds A beta(1-40) in a surfactant-like manner and counteracts the formation of all types of A beta(1-40) and A beta(1-42) aggregates. On the basis of these and previous findings, we are able to rationalize the molecular mechanisms of action of nonspecific modulators of protein self-assembly in terms of hydrophobic attraction and the conformational preferences of the polypeptide.

Published in

2012, volume: 51, number: 1, pages: 126-137

Authors' information

Lendel, Christofer
Swedish University of Agricultural Sciences, Department of Molecular Biology

UKÄ Subject classification

Biochemistry and Molecular Biology

Publication Identifiers


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