Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Diagnostic Center of Vascular Ultrasound, Beijing, China.
Curr Neuropharmacol. 2022 Aug 3;20(9):1651-1666. doi: 10.2174/1570159X19666210729123137.
Hypoxia-inducible factor-1 (HIF-1) is a heterodimer protein composed of an oxygenregulated functional subunit, HIF-1α, and a structural subunit, HIF-1β, belonging to the basic helixloop- helix family. Strict regulation of HIF-1 protein stability and subsequent transcriptional activity involves various molecular interactions and is primarily controlled by post-transcriptional modifications. Hypoxia, owing to impaired cerebral blood flow, has been implicated in a range of central nervous system (CNS) diseases by exerting a deleterious effect on brain function. As a master oxygen- sensitive transcription regulator, HIF-1 is responsible for upregulating a wide spectrum of target genes involved in glucose metabolism, angiogenesis, and erythropoiesis to generate the adaptive response to avoid, or at least minimize, hypoxic brain injury. However, prolonged, severe oxygen deprivation may directly contribute to the role-conversion of HIF-1, namely, from neuroprotection to the promotion of cell death. Currently, an increasing number of studies support the fact HIF-1 is involved in a variety of CNS-related diseases, such as intracranial atherosclerosis, stroke, and neurodegenerative diseases. This review article chiefly focuses on the effect of HIF-1 on the pathogenesis and mechanism of progression of numerous CNS-related disorders by mediating the expression of various downstream genes and extensive biological functional events and presents robust evidence that HIF-1 may represent a potential therapeutic target for CNS-related diseases.
缺氧诱导因子-1（HIF-1）是一种异二聚体蛋白，由氧调节的功能性亚基 HIF-1α和结构亚基 HIF-1β组成，属于碱性螺旋-环-螺旋家族。HIF-1 蛋白稳定性和随后的转录活性的严格调节涉及各种分子相互作用，主要受转录后修饰控制。由于脑血流受损，缺氧与一系列中枢神经系统（CNS）疾病有关，对脑功能产生有害影响。作为一个主要的氧敏感转录调节因子，HIF-1 负责上调广泛的参与葡萄糖代谢、血管生成和红细胞生成的靶基因，以产生适应反应，避免或至少最小化缺氧性脑损伤。然而，长时间、严重的缺氧可能直接导致 HIF-1 的角色转换，即从神经保护作用转变为促进细胞死亡。目前，越来越多的研究支持 HIF-1 参与多种与中枢神经系统相关的疾病，如颅内动脉粥样硬化、中风和神经退行性疾病。这篇综述文章主要关注 HIF-1 通过调节各种下游基因的表达和广泛的生物学功能事件对许多与中枢神经系统相关的疾病的发病机制和进展的影响，并提供了强有力的证据表明 HIF-1 可能代表与中枢神经系统相关的疾病的潜在治疗靶点。
