07-142025
Nature Communications | Liu Cong and Collaborators Discover That O-Glycopeptides Remodel Aβ Aggregation and Attenuate Its Neurotoxicity
This study reports that a tyrosine O-glycosylated peptide with a specific β-N-acetylgalactosamine (β-GalNAc) modification can co-assemble with Aβ42, accelerating the formation of novel amyloid fibril structures that reduce toxic oligomer accumulation and alleviate neurotoxicity. The team designed a series of O-glycosylated peptides based on the Aβ aggregation core fragment (Gly9–Ala21), incorporating diverse monosaccharide units and glycosidic linkages, to evaluate their effects on Aβ42 aggregation. Screening identified β-GalNAc–modified Aβ9–21 (4b) as a strong promoter of Aβ42 fibril formation, while reducing the build-up of toxic oligomers (Figure 1), indicating a shift toward low-toxicity aggregates.
