Davis, C.K., Jain, S.A., Bae, O.-N. et al. (2 more authors) (2019) Hypoxia mimetic agents for ischemic stroke. Frontiers in Cell and Developmental Biology, 6. 175. ISSN 2296-634X
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Davis, Jain, Bae, Majid and Rajanikant. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. http://creativecommons.org/licenses/by/4.0/ |
Keywords: | hypoxia-inducible factor-1; ischemic stroke; neuroprotection; iron chelators; hypoxia mimetic agent |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Mar 2019 10:05 |
Last Modified: | 12 Mar 2019 15:01 |
Published Version: | https://doi.org/10.3389/fcell.2018.00175 |
Status: | Published |
Publisher: | Frontiers Media |
Refereed: | Yes |
Identification Number: | 10.3389/fcell.2018.00175 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:142938 |
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