title: Hypoxia inducible factor-1 as a target for neurodegenerative diseases.
abstract: 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).
authors.affiliation: Department of Pharmacology & Toxicology, University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: Y
authors.initials: Y
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: ShiDu Yan
authors.forename: H
authors.initials: H
authors.lastname: Shi
mesh_terms: D005942:Gluconates / Q000627:therapeutic use; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational
chemical_list: D005942:Gluconates; D051793:Hypoxia-Inducible Factor 1; D007502:Iron Chelating Agents; C008229:2-ketogluconate