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Hypoxia Inducible Factor 1 as a Therapeutic Target in Ischemic Stroke

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Abstract:

In stroke research, a significant focus is to develop therapeutic strategies that prevent neuronal death and improve recovery. Yet, few successful therapeutic strategies have emerged. Hypoxia-inducible factor 1 (HIF-1) is a key regulator in hypoxia. It has been suggested to be an important player in neurological outcomes following ischemic stroke due to the functions of its downstream genes. These include genes that promote glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Many lines of evidence have shown that HIF-1 is induced in ischemic brains. Importantly, it seems that HIF-1 is primarily induced in the salvageable tissue of an ischemic brain, penumbra. However, the effect of HIF-1 on neuronal tissue injuries is still debatable based on evidence from in vitro and preclinical studies. Furthermore, it is of importance to understand the mechanism of HIF-1 degradation after its induction in ischemic brain. This review provides a present understanding of the mechanism of HIF-1 induction in ischemic neurons and the potential effect of HIF-1 on ischemic brain tissue. The author also elaborates on potential therapeutic approaches through understanding of the induction mechanism and of the potential role of HIF-1 in ischemic stroke.

Keywords: HIF-1; antioxidant; cerebral ischemia; free radical; neuroprotection; stroke

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709789760779

Affiliations: Department of Pharmacology and Toxicology, University of Kansas, School of Pharmacy, 1251 Wescoe Hall Drive, Malott Hall 5044, Lawrence, KS 66045, USA.

Publication date: December 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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