A cationic amphiphilic peptide chaperone rescues Aβ aggregation and cytotoxicity.

Directing Aβ to adopt a conformation that is free from aggregation and cell toxicity is an attractive and viable strategy to design therapeutics for Alzheimer's disease. Over the years, extensive efforts have been made to disrupt the aggregation of Aβ using various types of inhibitors but with limited success. Herein, we report the inhibition of aggregation of Aβ and disintegration of matured fibrils of Aβ into smaller assemblies by a 15-mer cationic amphiphilic peptide. The biophysical analysis comprising thioflavin T (ThT) mediated amyloid aggregation kinetic analysis, dynamic light scattering, ELISA, AFM, and TEM suggested that the peptide effectively disrupts Aβ aggregation. The circular dichroism (CD) and 2D-NMR HSQC analysis reveal that upon interaction, the peptide induces a conformational change in Aβ that is free from aggregation. Further, the cell assay experiments revealed that this peptide is non-toxic to cells and also rescues the cells from the toxicity of Aβ. Peptides with a shorter length displayed either weak or no inhibitory effect on Aβ aggregation and cytotoxicity. These results suggest that the 15-residue cationic amphiphilic peptide reported here may serve as a potential therapeutic candidate for Alzheimer's disease.