Pro-drug peptide and its metabolites disrupt amyloid fibrils
Channel: ISCB-SC Webinars
Date: 2021-03-23

The most common age-related neurodegenerative disorder, Alzheimer’s disease, is clinically characterized by continuous neuronal loss resulting in loss of memory and dementia with no cure to date. Amyloid-β (Aβ) aggregates and tau protein are believed to be the causative agents of this pathogenesis. In the present study, we have investigated the effect of the Pro-Drug peptide (Ac–LD(OBzl)FFD–NH2) and its metabolites (α-aspartyl & β-aspartyl) on the Aβ aggregates using atomistic molecular dynamics simulations. One of the key findings in our work is that in the presence of α & β aspartyl as a ligand, the salt bridges which hold the protofilaments of Aβ aggregate together are completely disrupted, thus setting the N-terminals of the Aβ strands free and exposed entirely to the solvent which makes the aggregation less severe.