Unveiling the Impact of Oxidation-driven Endogenous Protein Interactions on the Dynamics of Amyloid-β Aggregation and Toxicity

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 May 26

PMID 37234895

Authors

Zhi Du

Eunju Nam

Yuxi Lin

Mannkyu Hong

Tamas Molnar

Ikufumi Kondo

Koichiro Ishimori

Mu-Hyun Baik

Young-Ho Lee

Mi Hee Lim

Affiliations

Soon will be listed here.

Abstract

Cytochrome (Cyt ), 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 and amyloid-β (Aβ) with the consequent impact on the aggregation and toxicity of Aβ is not known. Here we report that Cyt 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 (HO), Cyt redirects Aβ peptides into less toxic, off-pathway amorphous aggregates, whereas without HO, it promotes Aβ fibrillization. The mechanisms behind these effects may involve a combination of the complexation between Cyt and Aβ, the oxidation of Aβ by Cyt and HO, and the modification of Cyt by HO. Our findings demonstrate a new function of Cyt as a modulator against Aβ amyloidogenesis.

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