FAHD1通过调节R-loop和cGAS-STING通路阻止神经元铁下垂。

IF 1.6 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Open Medicine Pub Date : 2025-09-24 eCollection Date: 2025-01-01 DOI:10.1515/med-2025-1200
Bitao Wang, Yubiao Yang, Zhi Zeng, Boyuan Ma, Yuxuan Zhou, Zhenhan Li, Jinyu Chen, Cheng Tang, Jian Hao, Xianhu Zhou
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引用次数: 0

摘要

背景:上铁坏死是一种铁依赖性脂质过氧化诱导的神经元死亡,与各种神经系统疾病的发生和进展密切相关,包括神经退行性疾病和中枢神经系统损伤。尽管在这一领域进行了大量的研究,但由于这些疾病的复杂病理生理机制,大多数可用的治疗策略在很大程度上仍然无效。此外,神经元铁下垂的机制尚未完全阐明。方法:通过生物信息学分析和细胞实验,探讨FAHD1在大鼠神经元铁凋亡中的作用。采用免疫荧光和点印迹分析探讨FAHD1过表达对R-loop形成的影响。此外,western blotting用于评估FAHD1过表达导致的cGAS-STING通路相关蛋白表达的变化。结果:我们的研究结果表明,氧化应激下的原代神经元中FAHD1的表达显著下调。此外,铁下垂似乎是氧化应激引发的神经元损伤的主要原因。过表达FAHD1可显著降低活性氧积累和r环形成,保持基因组稳定性,并通过抑制cGAS-STING通路的激活抑制神经元铁下垂。结论:FAHD1是神经元铁凋亡的重要调控因子,可能是治疗神经退行性疾病和中枢神经系统损伤的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS-STING pathway.

Background: Ferroptosis, a type of iron-dependent lipid peroxidation-induced neuronal death, has been strongly implicated in the initiation and progression of various neurological disorders, including neurodegenerative diseases and central nervous system (CNS) injuries. Although significant research efforts have been devoted to this area, most available therapeutic strategies remain largely ineffective due to the complex pathophysiology of these conditions. Moreover, the mechanisms underlying neuronal ferroptosis are not yet fully elucidated.

Methods: To investigate the role of FAHD1 in neuronal ferroptosis, bioinformatic analyses and cellular experiments were performed. Immunofluorescence and dot blot analyses were employed to explore the effects of FAHD1 overexpression on R-loop formation. Additionally, western blotting was used to assess alterations in the expression of cGAS-STING pathway-related proteins resulting from FAHD1 overexpression.

Results: Our results demonstrate that FAHD1 expression is significantly downregulated in primary neurons subjected to oxidative stress. Furthermore, ferroptosis appears to be a major contributor to neuronal damage triggered by oxidative stress. Overexpression of FAHD1 significantly reduced reactive oxygen species accumulation and R-loop formation, preserved genomic stability, and suppressed neuronal ferroptosis by inhibiting activation of the cGAS-STING pathway.

Conclusion: FAHD1 is a critical regulator of neuronal ferroptosis and may serve as a potential therapeutic target for the treatment of neurodegenerative diseases and CNS injuries.

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来源期刊
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
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