Early diagnosis and treatment of Alzheimer's disease by targeting toxic soluble Aβ oligomers.

ABSTRACT: Transient soluble oligomers of amyloid-β (Aβ) are toxic and accumulate early prior to insoluble plaque formation and cognitive impairment in Alzheimer's disease (AD). Synthetic cyclic D,L-α-peptides (e.g., 1) self-assemble into cross β-sheet nanotubes, react with early Aβ species (1-3 mers), and inhibit Aβ aggregation and toxicity in stoichiometric concentrations, in vitro. Employing a semicarbazide as an aza-glycine residue with an extra hydrogen-bond donor to tune nanotube assembly and amyloid engagement, [azaGly⁶]-1 inhibited Aβ aggregation and toxicity at substoichiometric concentrations. High-resolution NMR studies revealed dynamic interactions between [azaGly⁶]-1 and Aβ42 residues F19 and F20, which are pivotal for early dimerization and agg

SUBMITTER: Habashi M 

PROVIDER: S-EPMC9894226 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature