Rodriguez Juan, Li Tao, Xu Yiran, Sun Yanyan, Zhu Changlian
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Neural Regen Res. 2021 Feb;16(2):205-213. doi: 10.4103/1673-5374.290875.
Perinatal complications, such as asphyxia, can cause brain injuries that are often associated with subsequent neurological deficits, such as cerebral palsy or mental retardation. The mechanisms of perinatal brain injury are not fully understood, but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the mitochondrion. Among these proteins, apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia, but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain injury. In this review, we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy, specifically on the importance of apoptosis-inducing factor. The relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality, especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress, acting as a free radical scavenger. We also discuss all the different apoptosis-inducing factor isoforms discovered, focusing especially on apoptosis-inducing factor 2, which is only expressed in the brain and the functions of which are starting now to be clarified. Finally, we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions (pro-survival and pro-apoptotic) and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.
围产期并发症，如窒息，可导致脑损伤，这些损伤通常与随后的神经功能缺损有关，如脑瘫或智力迟钝。围产期脑损伤的机制尚未完全了解，但线粒体起着重要作用，这不仅是因为它们在新陈代谢中具有核心功能，还因为许多具有凋亡相关功能的蛋白质位于线粒体中。在这些蛋白质中，凋亡诱导因子已被证明是缺氧缺血后神经元细胞死亡的一个重要因素，但为了在围产期脑损伤的早期阶段开发更有效的治疗方法，需要更好地了解这些过程背后的机制。在这篇综述中，我们重点关注缺氧缺血性脑病的分子机制，特别是凋亡诱导因子的重要性。凋亡诱导因子的相关性不仅基于它参与不依赖半胱天冬酶的凋亡途径，还基于它在线粒体能量功能中起关键作用，特别是在氧化磷酸化过程中维持电子传递以及在氧化应激中作为自由基清除剂。我们还讨论了发现的所有不同的凋亡诱导因子异构体，特别关注仅在大脑中表达且其功能刚刚开始得到阐明的凋亡诱导因子2。最后，我们总结了凋亡诱导因子与几种蛋白质的相互作用，这些蛋白质对凋亡诱导因子的功能（促生存和促凋亡）至关重要，并且对于开发有前景的治疗靶点以改善围产期脑损伤后的预后非常重要。
