Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Hypoxia Mimetic Agents for Ischemic Stroke. Front Cell Dev Biol 2018;6:175

Date

01/24/2019

Pubmed ID

30671433

Pubmed Central ID

PMC6331394

DOI

10.3389/fcell.2018.00175

Scopus ID

2-s2.0-85073118145 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

Every year stroke claims more than 6 million lives worldwide. The majority of them are ischemic stroke. Small molecule-based therapeutics for ischemic stroke has attracted a lot of attention, but none has been shown to be clinically useful so far. Hypoxia-inducible factor-1 (HIF-1) plays a crucial role in the transcriptional adaptation of cells to hypoxia. Small molecule-based hypoxia-mimetic agents either stabilize HIF-1α via HIF-prolyl hydroxylases (PHDs) inhibition or through other mechanisms. In both the cases, these agents have been shown to confer ischemic neuroprotection in vitro and in vivo. The agents which act via PHD inhibition are mainly classified into iron chelators, iron competitors, and 2 oxoglutarate (2OG) analogs. This review discusses HIF structure and key players in the HIF-1 degradation pathway as well as the genes, proteins and chemical molecules that are connected to HIF-1 and how they affect cell survival following ischemic injury. Furthermore, this review gives a summary of studies that used PHD inhibitors and other HIF-1α stabilizers as hypoxia-mimetic agents for the treatment of ischemic injury.

Author List

Davis CK, Jain SA, Bae ON, Majid A, Rajanikant GK

Author

Carley Davis MD Professor in the Urologic Surgery department at Medical College of Wisconsin