Sammanfattning

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.

Publicerad i

Biochemistry
2012, Volym: 51, nummer: 1, sidor: 126-137
Utgivare: AMER CHEMICAL SOC

SLU författare

• Lendel, Christofer

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Biokemi och molekylärbiologi


Publikationens identifierare

DOI: https://doi.org/10.1021/bi201745g

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/41039