Emergence of Alternative Structures in Amyloid Beta 1-42 Monomeric Landscape by N-terminal Hexapeptide Amyloid Inhibitors.

ABSTRACT: Alzheimer's disease (AD) is characterized by deposition of amyloid beta (Aβ) peptides into senile plaques in the brain. While most familial mutations are associated with early-onset AD, recent studies report the AD-protective nature of two genetic human Aβ variants, i.e. A2T and A2V, in the heterozygous state. The mixture of A2V Aβ1-6 (Aβ₆) hexapeptide and WT Aβ1-42 (Αβ₄₂) is also found neuroprotective. Motivated by these findings, in this study we investigate the effects of WT, A2V, and A2T Aβ₆ hexapeptide binding on the monomeric WT Aβ₄₂ landscape. For this purpose, we have performed extensive atomistic Replica Exchange Molecular Dynamics simulations, elucidating preferential binding of Aβ₄₂ with the A2V and A2T hexapeptides compared

SUBMITTER: Chakraborty S 

PROVIDER: S-EPMC5577341 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature