Interaction between amyloid beta peptide and an aggregation blocker peptide mimicking islet amyloid polypeptide

31Citations
Citations of this article
66Readers
Mendeley users who have this article in their library.

Abstract

Assembly of amyloid-beta peptide (Aβ) into cytotoxic oligomeric and fibrillar aggregates is believed to be a major pathologic event in Alzheimer's disease (AD) and interfering with Aβ aggregation is an important strategy in the development of novel therapeutic approaches. Prior studies have shown that the double N-methylated analogue of islet amyloid polypeptide (IAPP) IAPP-GI, which is a conformationally constrained IAPP analogue mimicking a non-amyloidogenic IAPP conformation, is capable of blocking cytotoxic self-assembly of Aβ. Here we investigate the interaction of IAPP-GI with Aβ40 and Aβ42 using NMR spectroscopy. The most pronounced NMR chemical shift changes were observed for residues 13-20, while residues 7-9, 15-16 as well as the C-terminal half of Aβ - that is both regions of the Aβ sequence that are converted into β-strands in amyloid fibrils - were less accessible to solvent in the presence of IAPP-GI. At the same time, interaction of IAPP-GI with Aβ resulted in a concentration-dependent co-aggregation of Aβ and IAPP-GI that was enhanced for the more aggregation prone Aβ42 peptide. On the basis of the reduced toxicity of the Aβ peptide in the presence of IAPP-GI, our data are consistent with the suggestion that IAPP-GI redirects Aβ into nontoxic "off-pathway" aggregates. © 2011 Rezaei-Ghaleh et al.

Cite

CITATION STYLE

APA

Rezaei-Ghaleh, N., Andreetto, E., Yan, L. M., Kapurniotu, A., & Zweckstetter, M. (2011). Interaction between amyloid beta peptide and an aggregation blocker peptide mimicking islet amyloid polypeptide. PLoS ONE, 6(5). https://doi.org/10.1371/journal.pone.0020289

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free