Aromatic small molecules remodel toxic soluble oligomers of amyloid beta through three independent pathways.

ABSTRACT: In protein conformational disorders ranging from Alzheimer to Parkinson disease, proteins of unrelated sequence misfold into a similar array of aggregated conformers ranging from small oligomers to large amyloid fibrils. Substantial evidence suggests that small, prefibrillar oligomers are the most toxic species, yet to what extent they can be selectively targeted and remodeled into non-toxic conformers using small molecules is poorly understood. We have evaluated the conformational specificity and remodeling pathways of a diverse panel of aromatic small molecules against mature soluble oligomers of the Aβ42 peptide associated with Alzheimer disease. We find that small molecule antagonists can be grouped into three classes, which we herein define as Class I, II, and III molecules, based on

SUBMITTER: Ladiwala AR 

PROVIDER: S-EPMC3030325 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature