NOX4-mediated astrocyte ferroptosis in Alzheimer's disease

This study investigates NADPH Oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer's Disease (AD) using single-cell Sequencing data and transcriptomes. We analyzed AD single-cell RNA Sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4's role in Ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic Ferroptosis in AD. Silencing NOX4 mitigated Ferroptosis, improved cognition, reduced Aβ and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic Ferroptosis, underscoring its significance in AD progression.

Alzheimer’s disease; Astrocytes; Differential gene analysis; Ferroptosis; Immunofluorescence staining; Mouse model validation; NADPH oxidase 4; Single-cell sequencing.