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Hypoxia mimetic agents for ischemic stroke

Title
Hypoxia mimetic agents for ischemic stroke
Author
배옥남
Keywords
hypoxia-inducible factor-1; ischemic stroke; neuroprotection; iron chelators; hypoxia mimetic agent
Issue Date
2019-01
Publisher
Frontiers Media S.A.
Citation
Frontiers in Cell and Developmental Biology, v. 6, Article no. UNSP 175
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-1 alpha 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-1 alpha stabilizers as hypoxia-mimetic agents for the treatment of ischemic injury.
URI
https://www.frontiersin.org/articles/10.3389/fcell.2018.00175/fullhttp://repository.hanyang.ac.kr/handle/20.500.11754/112169
ISSN
2296-634X
DOI
10.3389/fcell.2018.00175
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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