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Title: KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletion
Authors: Kinoshita, Hisanori
Maki, Takakuni
Yasuda, Ken
Kishida, Natsue
Sasaoka, Norio
Takagi, Yasushi
Kakizuka, Akira
Takahashi, Ryosuke
Author's alias: 木下, 久徳
眞木, 崇州
笹岡, 紀男
垣塚, 彰
高橋, 良輔
Issue Date: 8-Aug-2019
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 9
Thesis number: 11519
Abstract: Reduced adenosine triphosphate (ATP) levels in ischemic stroke constitute an upstream contributor to neuronal cell death. We have recently created a small chemical, named Kyoto University Substance 121 (KUS121), which can reduce cellular ATP consumption. In this study, we examined whether KUS121 has neuroprotective effects in rodent cerebral ischemia models. We evaluated cell viability and ATP levels in vitro after oxygen glucose deprivation (OGD) in rat cortical primary neuronal cultures incubated with or without KUS121. We found that KUS121 protected neurons from cell death under OGD by preventing ATP depletion. We also used in vivo ischemic stroke models of transient distal middle cerebral artery occlusion in C57BL/6 and B-17 mice. Administration of KUS121 in these models improved functional deficits and reduced brain infarction volume after transient focal cerebral ischemia in both C57BL/6 and B-17 mice. These results indicate that KUS121 could be a novel type of neuroprotective drug for ischemic stroke.
Rights: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/245673
DOI(Published Version): 10.1038/s41598-019-47993-w
PubMed ID: 31395936
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