Lendel, Christofer
- Department of Molecular Biology, Swedish University of Agricultural Sciences
Abstract
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
Biochemistry
2012, volume: 51, number: 1, pages: 126-137
Publisher: AMER CHEMICAL SOC
SLU Authors
UKÄ Subject classification
Molecular Biology
Biochemistry
Publication identifier
- DOI: https://doi.org/10.1021/bi201745g
Permanent link to this page (URI)
https://res.slu.se/id/publ/41039