Hypoxia inducible factor-1 as a target for neurodegenerative diseases

Z. Zhang, J. Yan, Y. Chang, S. ShiDu Yan, H. Shi

Research output: Contribution to journalReview articlepeer-review

131 Scopus citations


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 β 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).

Original languageEnglish (US)
Pages (from-to)4335-4343
Number of pages9
JournalCurrent medicinal chemistry
Issue number28
StatePublished - Oct 2011
Externally publishedYes


  • 2-oxoglutarate analogues
  • AD
  • ALS
  • Cobalt
  • EPO
  • HD
  • HIF-1
  • Iron chelator
  • PD
  • Prolyl hydroxylase inhbitor
  • Protein modification
  • VEGF

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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