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铁死亡调控通过 Nrf2 及其对神经退行性疾病的影响。

Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.

机构信息

School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, People's Republic of China.

Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, 421001, People's Republic of China.

出版信息

Arch Toxicol. 2024 Mar;98(3):579-615. doi: 10.1007/s00204-023-03660-8. Epub 2024 Jan 24.


DOI:10.1007/s00204-023-03660-8
PMID:38265475
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10861688/
Abstract

This article provides an overview of the background knowledge of ferroptosis in the nervous system, as well as the key role of nuclear factor E2-related factor 2 (Nrf2) in regulating ferroptosis. The article takes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as the starting point to explore the close association between Nrf2 and ferroptosis, which is of clear and significant importance for understanding the mechanism of neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links ferroptosis to the pathogenesis of NDs. As the disease progresses, damage to the antioxidant system, excessive OS, and altered Nrf2 expression levels, especially the inhibition of ferroptosis by lipid peroxidation inhibitors and adaptive enhancement of Nrf2 signaling, demonstrate the potential clinical significance of Nrf2 in detecting and identifying ferroptosis, as well as targeted therapy for neuronal loss and mitochondrial dysfunction. These findings provide new insights and possibilities for the treatment and prevention of NDs.

摘要

本文概述了铁死亡在神经系统中的背景知识,以及核因子 E2 相关因子 2(Nrf2)在调节铁死亡中的关键作用。本文以阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩侧索硬化症(ALS)为起点,探讨了 Nrf2 与铁死亡之间的密切关联,这对于理解基于氧化应激(OS)的神经退行性疾病(NDs)的机制具有明确而重要的意义。越来越多的证据将铁死亡与 NDs 的发病机制联系起来。随着疾病的进展,抗氧化系统受损、过度的 OS 和 Nrf2 表达水平改变,特别是脂质过氧化抑制剂抑制铁死亡和适应性增强 Nrf2 信号,表明 Nrf2 在检测和识别铁死亡以及针对神经元丢失和线粒体功能障碍的靶向治疗方面具有潜在的临床意义。这些发现为 NDs 的治疗和预防提供了新的思路和可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61a/10861688/3191f9a74d37/204_2023_3660_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61a/10861688/f41ea98c0206/204_2023_3660_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61a/10861688/bede619fd321/204_2023_3660_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61a/10861688/3191f9a74d37/204_2023_3660_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61a/10861688/f41ea98c0206/204_2023_3660_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61a/10861688/bede619fd321/204_2023_3660_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61a/10861688/3191f9a74d37/204_2023_3660_Fig3_HTML.jpg

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引用本文的文献

[1]
NOX-NOS crosstalk in the liver-brain axis: Novel insights for redox regulation and neurodegenerative diseases.

Redox Biol. 2025-8-6

[2]
DHODH-mediated mitochondrial redox homeostasis: a novel ferroptosis regulator and promising therapeutic target.

Redox Biol. 2025-7-23

[3]
Iron dysregulation, ferroptosis, and oxidative stress in diabetic osteoporosis: Mechanisms, bone metabolism disruption, and therapeutic strategies.

World J Diabetes. 2025-6-15

[4]
Edaravone dexborneol protected neurological function by targeting NRF2/ARE and NF-κB/AIM2 pathways in cerebral ischemia/reperfusion injury.

Front Pharmacol. 2025-4-25

[5]
Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration.

Biomedicines. 2025-4-17

[6]
Ferroptosis in NAFLD: insights and the therapeutic potential of exercise.

Front Med (Lausanne). 2025-3-26

[7]
Nrf2/Bach1 signaling axis: A promising multifaceted therapeutic strategy for Alzheimer's disease.

Neurotherapeutics. 2025-4

[8]
Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.

Biomedicines. 2025-1-31

[9]
Targeting natural antioxidant polyphenols to protect neuroinflammation and neurodegenerative diseases: a comprehensive review.

Front Pharmacol. 2025-1-24

[10]
Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress.

Front Pharmacol. 2025-2-3

本文引用的文献

[1]
Neuroprotection of NRF2 against Ferroptosis after Traumatic Brain Injury in Mice.

Antioxidants (Basel). 2023-3-16

[2]
Fighting age-related orthopedic diseases: focusing on ferroptosis.

Bone Res. 2023-3-1

[3]
Ferroptosis in neurodegenerative diseases: inhibitors as promising candidate mitigators.

Eur Rev Med Pharmacol Sci. 2023-1

[4]
Nrf2 Pathway in Huntington's Disease (HD): What Is Its Role?

Int J Mol Sci. 2022-12-3

[5]
Dimethyl fumarate protects against hepatic ischemia-reperfusion injury by alleviating ferroptosis via the NRF2/SLC7A11/HO-1 axis.

Cell Cycle. 2023-4

[6]
Role of Nrf2 in aging, Alzheimer's and other neurodegenerative diseases.

Ageing Res Rev. 2022-12

[7]
A non-canonical vitamin K cycle is a potent ferroptosis suppressor.

Nature. 2022-8

[8]
Role of Nrf2 in Parkinson's Disease: Toward New Perspectives.

Front Pharmacol. 2022-6-24

[9]
The Interaction of and in Neurogenesis and Its Implication in Neurodegenerative Diseases.

Cells. 2022-6-28

[10]
Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications.

Cell. 2022-7-7

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