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铁死亡机制在神经疾病中的关键作用及靶向治疗前景

The key role of the ferroptosis mechanism in neurological diseases and prospects for targeted therapy.

作者信息

Xie Chenyu, Wu Nan, Guo Jiaojiao, Ma Liangliang, Zhang Congcong

机构信息

Department of Rehabilitation, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.

Rehabilitation Medicine College, Henan University of Chinese Medicine, Zhengzhou, Henan, China.

出版信息

Front Neurosci. 2025 May 12;19:1591417. doi: 10.3389/fnins.2025.1591417. eCollection 2025.


DOI:10.3389/fnins.2025.1591417
PMID:40421132
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12104224/
Abstract

Neurological disorders represent a major global health concern owing to their intricate pathological processes. Ferroptosis, defined as a form of cell death that is reliant on iron, has been closely linked to various neurological conditions. The fundamental process underlying ferroptosis is defined by the excessive buildup of iron ions, which initiates lipid peroxidation processes leading to cellular demise. Neurons, as highly metabolically active cells, are susceptible to oxidative stress, and imbalances in iron metabolism can directly initiate the ferroptosis process. In neurodegenerative disorders like Alzheimer's disease and Parkinson's disease, ferroptosis driven by iron accumulation represents a fundamental pathological connection. Although the connection between ferroptosis and neurological diseases is clear, clinical application still faces challenges, such as precise regulation of iron metabolism, development of specific drugs, and assessment of efficacy. The limited comprehension of the ferroptosis mechanism hinders the development of personalized treatment approaches. Consequently, subsequent investigations must tackle these obstacles to facilitate the clinical application of ferroptosis-associated therapies in neurological disorders. This article provides a comprehensive overview of the most recent advancements regarding the underlying mechanisms of ferroptosis. Subsequently, the study investigates the mechanistic contributions of ferroptosis within the nervous system. In conclusion, we evaluate and deliberate on targeted therapeutic strategies associated with ferroptosis and neurological disorders.

摘要

由于其复杂的病理过程,神经系统疾病是全球主要的健康问题。铁死亡被定义为一种依赖铁的细胞死亡形式,它与各种神经系统疾病密切相关。铁死亡的基本过程是由铁离子的过度积累所定义的,铁离子的过度积累引发脂质过氧化过程,导致细胞死亡。神经元作为高代谢活性细胞,易受氧化应激影响,铁代谢失衡可直接引发铁死亡过程。在阿尔茨海默病和帕金森病等神经退行性疾病中,铁积累驱动的铁死亡代表了一种基本的病理联系。尽管铁死亡与神经系统疾病之间的联系很明显,但临床应用仍面临挑战,如铁代谢的精确调节、特定药物的开发以及疗效评估。对铁死亡机制的有限理解阻碍了个性化治疗方法的发展。因此,后续研究必须克服这些障碍,以促进铁死亡相关疗法在神经系统疾病中的临床应用。本文全面概述了铁死亡潜在机制的最新进展。随后,该研究探讨了铁死亡在神经系统中的作用机制。最后,我们评估并讨论了与铁死亡和神经系统疾病相关的靶向治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/12104224/c0c66faa1cf7/fnins-19-1591417-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/12104224/db20126e1b29/fnins-19-1591417-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/12104224/a1af8c5899c7/fnins-19-1591417-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/12104224/c0c66faa1cf7/fnins-19-1591417-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/12104224/db20126e1b29/fnins-19-1591417-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/12104224/a1af8c5899c7/fnins-19-1591417-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/12104224/c0c66faa1cf7/fnins-19-1591417-g003.jpg

相似文献

[1]
The key role of the ferroptosis mechanism in neurological diseases and prospects for targeted therapy.

Front Neurosci. 2025-5-12

[2]
Ferroptosis as a Therapeutic Target in Neurodegenerative Diseases: Exploring the Mechanisms and Potential of Treating Alzheimer's Disease and Parkinson's Disease.

Protein Pept Lett. 2024

[3]
Emerging Mechanisms and Targeted Therapy of Ferroptosis in Neurological Diseases and Neuro-oncology.

Int J Biol Sci. 2022-6-27

[4]
Role and mechanism of ferroptosis in neurological diseases.

Mol Metab. 2022-7

[5]
Targeting Ferroptosis in Rare Neurological Disorders Including Pediatric Conditions: Innovations and Therapeutic Challenges.

Biomedicines. 2025-1-22

[6]
Ferroptosis, a Recent Defined Form of Critical Cell Death in Neurological Disorders.

J Mol Neurosci. 2018-8-25

[7]
Understanding the Mechanism of Ferroptosis in Neurodegenerative Diseases.

Front Biosci (Landmark Ed). 2024-8-20

[8]
Advances in the study of ferroptosis and its relationship to autoimmune diseases.

Int Immunopharmacol. 2024-10-25

[9]
The role of ferroptosis in neurodegenerative diseases.

Front Cell Neurosci. 2024-10-15

[10]
Implications of liquid-liquid phase separation and ferroptosis in Alzheimer's disease.

Neuropharmacology. 2024-11-15

本文引用的文献

[1]
Taurine Attenuates Neuronal Ferroptosis by CSF-Derived Exosomes of GABABR Encephalitis Through GABABR/NF2/P-YAP Pathway.

Mol Neurobiol. 2025-3-14

[2]
Mito-TEMPO Ameliorates Sodium Palmitate Induced Ferroptosis in MIN6 Cells through PINK1/Parkin-Mediated Mitophagy.

Biomed Environ Sci. 2024-10-20

[3]
Inhibition of Aβ Aggregation and Tau Phosphorylation with Functionalized Biomimetic Nanoparticles for Synergic Alzheimer's Disease Therapy.

ACS Appl Mater Interfaces. 2024-11-13

[4]
[Knockdown of nuclear protein 1 delays pathological pro-gression of osteoarthritis through inhibiting chondrocyte ferroptosis].

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024-12-25

[5]
Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations.

Sci Adv. 2024-11

[6]
Generic Diagramming Platform (GDP): a comprehensive database of high-quality biomedical graphics.

Nucleic Acids Res. 2025-1-6

[7]
An insight into allele-selective approaches to lowering mutant huntingtin protein for Huntington's disease treatment.

Biomed Pharmacother. 2024-11

[8]
FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury.

Front Pharmacol. 2024-9-23

[9]
FOXO1-NCOA4 Axis Contributes to Cisplatin-Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy.

Adv Sci (Weinh). 2024-10

[10]
Spermidine mitigates ferroptosis in free fatty acid-induced AML-12 cells through the ATF4/SLC7A11/GCLM/GPX4 pathway.

Biochim Biophys Acta Mol Cell Biol Lipids. 2024-12

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