Department of Pharmacology & Toxicology, University of Kansas, Lawrence, Kansas 66045, USA.
Curr Med Chem. 2011;18(28):4335-43. doi: 10.2174/092986711797200426.
Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. HIF-1, a heterodimer consisting of a constitutively expressed β subunit and an oxygen-regulated α subunit, regulates a series of genes that participate in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. The activity of HIF-1 is controlled by post-translational modifications on different amino acid residues of its subunits, mainly the alpha subunit. Besides in ischemic stroke (see review [1]), emerging evidence has revealed that HIF-1 activity and expression of its down-stream genes, such as vascular endothelial growth factor and erythropoietin, are altered in a range of neurodegenerative diseases. At the same time, experimental and clinical evidence has demonstrated that regulating HIF-1 might ameliorate the cellular and tissue damage in the neurodegenerative diseases. These new findings suggest HIF-1 as a potential medicinal target for the neurodegenerative diseases. This review focuses on HIF-1α protein modifications and HIF-1's potential neuroprotective roles in Alzheimer's (AD), Parkinson's (PD), Huntington's diseases (HD), and amyotrophic lateral sclerosis (ALS).
缺氧诱导因子-1（HIF-1）是一种转录因子，负责细胞和组织对低氧张力的适应。HIF-1 由一个组成型表达的β亚基和一个氧调节的α亚基组成的异二聚体，调节一系列参与血管生成、铁代谢、葡萄糖代谢和细胞增殖/存活的基因。HIF-1 的活性受其亚基不同氨基酸残基的翻译后修饰控制，主要是α亚基。除了在缺血性中风中（见综述[1]），新出现的证据表明，HIF-1 活性及其下游基因（如血管内皮生长因子和促红细胞生成素）的表达在一系列神经退行性疾病中发生改变。同时，实验和临床证据表明，调节 HIF-1 可能改善神经退行性疾病中的细胞和组织损伤。这些新发现表明 HIF-1 可能成为神经退行性疾病的潜在治疗靶点。本综述重点介绍 HIF-1α 蛋白修饰以及 HIF-1 在阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和肌萎缩侧索硬化症（ALS）中的潜在神经保护作用。
