Interaction between DNA methylation and oxidative stress in Alzheimer's disease:Bidirectional regulation and positive-feedback networks
CHEN Zhiyi
LIU Sirui
HAN Jingxian
ZHANG Xuezhu
Abstract：Alzheimer's disease(AD)is a neurodegenerative disorder characterized by β-amyloid(Aβ)deposition and hyperphosphorylation of the Tau protein.Oxidative stress plays a pivotal role throughout its patho-logical progression.Recent studies have demonstrated that DNA methylation,a key epigenetic regulatory mecha-nism,interacts with oxidative stress to form a core network underlying AD pathogenesis.This review summarizes the molecular mechanisms through which aberrant DNA methylation in AD exacerbates oxidative damage by impair-ing antioxidant defenses,inducing mitochondrial dysfunction,and activating inflammatory pathways.Moreover,it examines the bidirectional interplay between oxidative stress and DNA methylation imbalance in AD:Oxidative stress depletes methyl donors,causes oxidative DNA lesions,and impairs the activity of epigenetic regulatory enzymes.The study aims to identify potential molecular diagnostic markers for early-stage AD and to provide novel insights and a theoretical basis for developing combined therapeutic strategies targeting both redox imbalance and epigenetic dysregulation.
Keywords：Alzheimer's diseaseDNA methylationoxidative stressAβ depositionTau pro-teinmitochondrion
Publication Date：2025-12-25
Online Publishing Date：2026-01-04(First online date of this platform, not the publication date of the document)
Pages：6( 3802-3807 )