%0 Journal Article
%T Tau Derived Hexapeptide AcPHF6 Promotes Beta-Amyloid (A¦Â) Fibrillogenesis
%J -
%D 2018
%R https://doi.org/10.1021/acschemneuro.7b00433
%X We studied the interactions of a tau derived hexapeptide AcPHF6 with ¦Â-amyloid peptides A¦Â40 and A¦Â42 which reveals its unusual ability to promote A¦Â fibrillogenesis. The results demonstrate that the N-acetylated and C-amidated AcPHF6 hexapeptide can cause significant acceleration in A¦Â40 and A¦Â42 fibril growth. Aggregation kinetic studies at pH 7.4 show that at 25 ¦ÌM, AcPHF6 hexapeptide was able to cause ¡«2.3-fold increase in A¦Â40 fibrillogenesis dramatically changing the aggregation kinetics. In addition, AcPHF6 peptide was able to reduce cellular toxicity mediated by A¦Â40 and A¦Â42 in hippocampal neuronal cell line (HT22). Computational studies suggest that the AcPHF6 peptide can act as an anchor and provides a hydrophobic surface for A¦Â monomer to bind and undergo rapid fibrillogenesis to form less toxic fibrils and alter the aggregation kinetics. At the molecular level we propose a ¡°dock-and-pack¡± mechanism where the AcPHF6 hexapeptide aggregates can stabilize the ¦Â-hairpin and promote rapid A¦Â self-assembly and growth to form less toxic oligomers or fibrils. Our results have direct implications in designing novel peptide/peptidomimetics as novel pharmacological tools to study protein aggregation and potentially prevent A¦Â-mediated toxicity in Alzheimer¡¯s disease
%U https://pubs.acs.org/doi/10.1021/acschemneuro.7b00433