阿尔茨海默病中由 NOX4 介导的星形胶质细胞铁蛋白沉积。

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell and Bioscience Pub Date : 2024-07-02 DOI:10.1186/s13578-024-01266-w

Yasenjiang Maimaiti, Ting Su, Zhanying Zhang, Lingling Ma, Yuan Zhang, Hong Xu

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引用次数: 0

摘要

本研究利用单细胞测序数据和转录组研究了 NADPH 氧化酶 4 (NOX4) 在阿尔茨海默病（AD）中参与铁介导的星形胶质细胞死亡的情况。我们分析了AD单细胞RNA测序数据，确定了星形胶质细胞标记基因，并探索了星形胶质细胞的生物学过程。我们将 AD 相关芯片数据与铁变态相关基因整合在一起，重点研究了 NOX4。我们在体外和体内验证了 NOX4 在铁变态反应和 AD 中的作用。星形胶质细胞标记基因在 AD 中富集，强调了它们的作用。NOX4是AD中星形胶质细胞铁突变的重要参与者。沉默NOX4可减轻铁突变，改善认知能力，降低Aβ和p-Tau水平，缓解线粒体异常。NOX4能促进星形胶质细胞的铁蛋白沉积，突出了它在AD进展过程中的重要性。

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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.

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来源期刊

Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

10.70

自引率

0.00%

发文量

187

审稿时长

>12 weeks

期刊介绍： Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.