Astrocytic mitochondrial frataxin-A promising target for ischemic brain injury.

Astrocytic mitochondrial frataxin-A promising target for ischemic brain injury.
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DOI:
10.1111/cns.14068
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发表时间:
2023-03
影响因子:
5.5
通讯作者:
--
中科院分区:
医学1区
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在缺血的大脑中,缺氧导致线粒体功能障碍、能量产生不足和星形胶质细胞激活。然而,大多数研究脑缺血中线粒体功能障碍的研究都只关注神经元。本综述将强调星形胶质细胞的形态、分子和功能异质性在脑损伤中的作用的重要性,并探讨活化的星形胶质细胞如何表现出钙失衡、活性氧过度产生和细胞凋亡。此外,还将特别关注缺血期间活化的星形胶质细胞中线粒体蛋白frataxin的作用及其在脑缺血的药理学治疗中的假定作用。星形胶质细胞将脑微血管与神经元互连。星形胶质细胞内的线粒体功能调节脑血管缺血期间的神经元反应。星形胶质细胞钙流入可能会减少 frataxin (FXN) 的表达,从而导致线粒体功能障碍。星形细胞 FXN 的靶向诱导可能是缺血性脑损伤的一种有吸引力的治疗策略。
In the ischemic brain, hypoxia leads to mitochondrial dysfunction, insufficient energy production, and astrocyte activation. Yet, most studies investigating mitochondrial dysfunction in cerebral ischemia have focused exclusively on neurons. This review will highlight the importance of the morphological, molecular, and functional heterogeneity of astrocytes in their role in brain injuries and explore how activated astrocytes exhibit calcium imbalance, reactive oxygen species overproduction, and apoptosis. In addition, special focus will be given to the role of the mitochondrial protein frataxin in activated astrocytes during ischemia and its putative role in the pharmacological management of cerebral ischemia. Astrocytes interconnect cerebral microvessels with neurons. Mitochondrial function within the astrocytes regulates neuronal response during cerebrovascular ischemia. Astrocytic calcium influx may reduce frataxin (FXN) expression, thereby contributing to mitochondrial dysfunction. Targeted induction of astrocytic FXN may be an attractive therapeutic strategy for ischemic brain injury.
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