NOX4-mediated astrocyte ferroptosis in Alzheimer's disease

  • Cell Biosci. 2024 Jul 2;14(1):88. doi: 10.1186/s13578-024-01266-w.
Yasenjiang Maimaiti  1 ,  Ting Su  2 ,  Zhanying Zhang  2 ,  Lingling Ma  2 ,  Yuan Zhang  2 ,  Hong Xu  3
Affiliations
  • 1. Gerontology Center, People's Hospital of Xinjiang Uygur Autonomous Region, No.91 Tianchi Road, Urumqi, Xinjiang, China. [email protected].
  • 2. Gerontology Center, People's Hospital of Xinjiang Uygur Autonomous Region, No.91 Tianchi Road, Urumqi, Xinjiang, China.
  • 3. Gerontology Center, People's Hospital of Xinjiang Uygur Autonomous Region, No.91 Tianchi Road, Urumqi, Xinjiang, China. [email protected].
PMID: 38956702 DOI: 10.1186/s13578-024-01266-w
Abstract

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.

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