CNS neuroscience & therapeutics · 2025
SFXN1 Reduction Alleviates Cerebral Ischemia-Reperfusion Injury by Promoting Neuronal Survival and Reducing Neuroinflammation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xu Xiangyu, Duan Zhongying, Zhou Xin, Zhao Rui, Xu Jing, Zhang Zhaolong, Lv Mengfei, Wan Qi, Cui Yu
Аннотация
AIM: Sideroflexin 1 (SFXN1) is an important inner mitochondrial membrane protein that regulates many physiological and pathological events. However, the role of SFXN1 in cerebral ischemia-reperfusion (I/R)-induced neuronal death remains unclear.
METHODS: We employed in vivo injury models of transient middle cerebral artery occlusion (tMCAO) and in vitro models of lipopolysaccharide (LPS) stimulation and oxygen-glucose deprivation/reperfusion (OGD/R) to investigate the regulatory effects of SFXN1 on neuroinflammation and brain injury. Western blotting, immunofluorescence, and real-time quantitative PCR were utilized to assess SFXN1 expression, proinflammatory signaling pathways activation, and cytokine levels in vitro. Cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Nissl staining.
RESULTS: SFXN1 expression was upregulated following cerebral I/R injury. Both neurons and microglia exhibited increased SFXN1 expression after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. SFXN1 knockdown reduced OGD/R-induced neuronal death and alleviated cerebral I/R injury. Additionally, conditioned medium from SFXN1-knockdown microglia reduced neurotoxicity in vitro. Mechanistically, SFXN1 induced mitochondrial dysfunction and neuronal death after OGD/R in an iron-independent manner. Furthermore, SFXN1 promoted the production of proinflammatory cytokines by promoting NF-κB activation, partially through iron transport in microglia after OGD/R.
CONCLUSION: This study reveals the novel role of SFXN1 in exacerbating cerebral I/R injury by reducing neuronal survival through the modulation of mitochondrial function and promotion of microglia-mediated neuroinflammation via NF-κB activation.
METHODS: We employed in vivo injury models of transient middle cerebral artery occlusion (tMCAO) and in vitro models of lipopolysaccharide (LPS) stimulation and oxygen-glucose deprivation/reperfusion (OGD/R) to investigate the regulatory effects of SFXN1 on neuroinflammation and brain injury. Western blotting, immunofluorescence, and real-time quantitative PCR were utilized to assess SFXN1 expression, proinflammatory signaling pathways activation, and cytokine levels in vitro. Cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Nissl staining.
RESULTS: SFXN1 expression was upregulated following cerebral I/R injury. Both neurons and microglia exhibited increased SFXN1 expression after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. SFXN1 knockdown reduced OGD/R-induced neuronal death and alleviated cerebral I/R injury. Additionally, conditioned medium from SFXN1-knockdown microglia reduced neurotoxicity in vitro. Mechanistically, SFXN1 induced mitochondrial dysfunction and neuronal death after OGD/R in an iron-independent manner. Furthermore, SFXN1 promoted the production of proinflammatory cytokines by promoting NF-κB activation, partially through iron transport in microglia after OGD/R.
CONCLUSION: This study reveals the novel role of SFXN1 in exacerbating cerebral I/R injury by reducing neuronal survival through the modulation of mitochondrial function and promotion of microglia-mediated neuroinflammation via NF-κB activation.