Mitochondrial dynamics in the neonatal brain - a potential target following injury?
Mitochondrial dynamics in the neonatal brain - a potential target following injury?
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DOI：
10.1042/bsr20211696
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发表时间：
2022-03-31
影响因子：
4
通讯作者：
Thornton C
中科院分区：
文献类型：
--
作者：
Jones A;Thornton C
出生窒息及其后遗症，缺氧缺血性（HI）脑损伤的影响，是长期和显着的，无论是对婴儿和他们的家庭。治疗选择仅限于治疗性低温，这种方法并不普遍成功，在资源匮乏的情况下也无法使用。脑血流中断后伴随神经元死亡的能量缺乏涉及线粒体功能障碍。这种HI损伤触发线粒体外膜透化，导致促凋亡蛋白释放到细胞溶质中和细胞死亡。最近，线粒体分裂和融合中的关键参与者已被确定为HI脑损伤后的靶点。这篇综述的目的是提供一个介绍的分子球员和途径驱动线粒体动力学，这些途径的调节，以及它们是如何改变HI损伤。最后，我们回顾了已经批准用于其他适应症的药物的再利用或重新定位的进展，这些药物可能针对线粒体动力学，并为脑损伤后的干预提供了有希望的途径。这种重新利用可以提供一种机制，以快速跟踪，低成本的治疗方案的诊所。
The impact of birth asphyxia and its sequelae, hypoxic–ischaemic (HI) brain injury, is long-lasting and significant, both for the infant and for their family. Treatment options are limited to therapeutic hypothermia, which is not universally successful and is unavailable in low resource settings. The energy deficits that accompany neuronal death following interruption of blood flow to the brain implicate mitochondrial dysfunction. Such HI insults trigger mitochondrial outer membrane permeabilisation leading to release of pro-apoptotic proteins into the cytosol and cell death. More recently, key players in mitochondrial fission and fusion have been identified as targets following HI brain injury. This review aims to provide an introduction to the molecular players and pathways driving mitochondrial dynamics, the regulation of these pathways and how they are altered following HI insult. Finally, we review progress on repurposing or repositioning drugs already approved for other indications, which may target mitochondrial dynamics and provide promising avenues for intervention following brain injury. Such repurposing may provide a mechanism to fast-track, low-cost treatment options to the clinic.