Revisiting the Benefits of Exercise for Alzheimer's Disease through the Lens of Ferroptosis: A New Perspective

被引:0
作者
Hao, Zikang [1 ]
Guo, Xinmeng [1 ]
Wu, Jiawen [2 ]
Yang, Guang [2 ]
机构
[1] Shandong Univ, Sch Phys Educ, Dept Sport & Hlth, Jinan, Peoples R China
[2] Nanjing Univ Chinese Med, Kunshan Hosp, Jiangsu, Peoples R China
来源
AGING AND DISEASE | 2025年
关键词
ferroptosis; exercise; Alzheimer's disease; oxidative stress; nrf2; OXIDATIVE STRESS; COGNITIVE IMPAIRMENT; LIPID-PEROXIDATION; IRON; NRF2; NEURODEGENERATION; METABOLISM; PREVENTION; PATHWAYS; GPX4;
D O I
10.14336/AD.2024.1560
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Ferroptosis, an iron-dependent form of programmed cell death driven by oxidative stress, plays a crucial role in the progression of Alzheimer's disease (AD). Aging diminishes antioxidant systems that maintain iron homeostasis, particularly affecting the glutathione peroxidase (GPX) system, leading to increased ferroptosis and exacerbated neurodegeneration and neuroinflammation in AD. Nuclear factor erythroid 2- related factor 2 (Nrf2) is a key transcription factor regulating genes involved in antioxidant defense and ferroptosis. In this review, we examine the interconnected roles of Nrf2 signaling, iron metabolism, and ferroptosis in AD, and discuss how regular physical exercise-known to enhance antioxidant capacity-might influence these processes. Despite evidence linking exercise to improved cognitive function in AD and its role in modulating oxidative stress, there is a paucity of research specifically addressing how exercise affects ferroptosis in the AD brain. To address this gap, we utilized bioinformatics techniques to identify potential pathways and mechanisms by which exercise may mitigate ferroptosis in AD through Nrf2 signaling. Analyzing gene expression profiles from the GEO database, we identified differentially expressed ferroptosis-related genes in the hippocampus following exercise intervention. Hub genes like SLC2A1, TXN, MEF2C, and KRAS were significantly upregulated, suggesting that exercise may activate a network enhancing antioxidant defenses and regulating iron metabolism via Nrf2. Our findings propose a novel mechanism whereby exercise alleviates abnormal ferroptosis in the AD brain through modulation of Nrf2 signaling. This study highlights the need for further research to validate these findings and explore exercise as a therapeutic strategy for AD by targeting ferroptosis.
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页数:16
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