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 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 language | English (US) |
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Pages (from-to) | 4335-4343 |
Number of pages | 9 |
Journal | Current medicinal chemistry |
Volume | 18 |
Issue number | 28 |
DOIs | |
State | Published - Oct 2011 |
Externally published | Yes |
Keywords
- 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