Issue 20, 2023

Unveiling the impact of oxidation-driven endogenous protein interactions on the dynamics of amyloid-β aggregation and toxicity

Abstract

Cytochrome c (Cyt c), a multifunctional protein with a crucial role in controlling cell fate, has been implicated in the amyloid pathology associated with Alzheimer's disease (AD); however, the interaction between Cyt c and amyloid-β (Aβ) with the consequent impact on the aggregation and toxicity of Aβ is not known. Here we report that Cyt c can directly bind to Aβ and alter the aggregation and toxicity profiles of Aβ in a manner that is dependent on the presence of a peroxide. When combined with hydrogen peroxide (H2O2), Cyt c redirects Aβ peptides into less toxic, off-pathway amorphous aggregates, whereas without H2O2, it promotes Aβ fibrillization. The mechanisms behind these effects may involve a combination of the complexation between Cyt c and Aβ, the oxidation of Aβ by Cyt c and H2O2, and the modification of Cyt c by H2O2. Our findings demonstrate a new function of Cyt c as a modulator against Aβ amyloidogenesis.

Graphical abstract: Unveiling the impact of oxidation-driven endogenous protein interactions on the dynamics of amyloid-β aggregation and toxicity

Supplementary files

Article information

Article type
Edge Article
Submitted
16 fev 2023
Accepted
24 apr 2023
First published
25 apr 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 5340-5349

Unveiling the impact of oxidation-driven endogenous protein interactions on the dynamics of amyloid-β aggregation and toxicity

Z. Du, E. Nam, Y. Lin, M. Hong, T. Molnár, I. Kondo, K. Ishimori, M. Baik, Y. Lee and M. H. Lim, Chem. Sci., 2023, 14, 5340 DOI: 10.1039/D3SC00881A

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