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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Hypoxia Inducible Factor-1 as a Target for Neurodegenerative Diseases

Author(s): Z. Zhang, J. Yan, Y. Chang, S. ShiDu Yan and H. Shi

Volume 18, Issue 28, 2011

Page: [4335 - 4343] Pages: 9

DOI: 10.2174/092986711797200426

Price: $65


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).

Keywords: AD, ALS, EPO, HD, HIF-1, PD, VEGF, protein modification, prolyl hydroxylase inhbitor, iron chelator, 2-oxoglutarate analogues, cobalt

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