A novel HIF inhibitor halofuginone prevents neurodegeneration in a murine model of retinal ischemia-reperfusion

Hiromitsu Kunimi; Yukihiro Miwa; Hiroyoshi Inoue; Kazuo Tsubota; Toshihide Kurihara

doi:10.3390/ijms20133171

A novel HIF inhibitor halofuginone prevents neurodegeneration in a murine model of retinal ischemia-reperfusion

Hiromitsu Kunimi, Yukihiro Miwa, Hiroyoshi Inoue, Kazuo Tsubota, Toshihide Kurihara

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.

Original language	English
Article number	3171
Journal	International journal of molecular sciences
Volume	20
Issue number	13
DOIs	https://doi.org/10.3390/ijms20133171
Publication status	Published - 2019 Jul 1

Keywords

HIF-1α
Halofuginone
Ischemia-reperfusion
Neuroprotection

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.3390/ijms20133171

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title = "A novel HIF inhibitor halofuginone prevents neurodegeneration in a murine model of retinal ischemia-reperfusion",

abstract = "Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.",

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author = "Hiromitsu Kunimi and Yukihiro Miwa and Hiroyoshi Inoue and Kazuo Tsubota and Toshihide Kurihara",

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AU - Miwa, Yukihiro

AU - Inoue, Hiroyoshi

AU - Tsubota, Kazuo

AU - Kurihara, Toshihide

N1 - Funding Information: Funding: This work was supported by Grants-in-Aid for Scientific Research (KAKENHI, number 15K10881 and 18K09424) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to Toshihide Kurihara. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.

AB - Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.

KW - HIF-1α

KW - Halofuginone

KW - Ischemia-reperfusion

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A novel HIF inhibitor halofuginone prevents neurodegeneration in a murine model of retinal ischemia-reperfusion

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Keywords

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