2. Academic Validation
  3. KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletion

KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletion

  • Sci Rep. 2019 Aug 8;9(1):11519. doi: 10.1038/s41598-019-47993-w.
Hisanori Kinoshita 1,  Takakuni Maki 2,  Ken Yasuda 1,  Natsue Kishida 3,  Norio Sasaoka 4,  Yasushi Takagi 3,  Akira Kakizuka 5,  Ryosuke Takahashi 1
Affiliations

Affiliations

  • 1 Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
  • 2 Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. harutoma@kuhp.kyoto-u.ac.jp.
  • 3 Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • 4 Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Kyoto, Japan.
  • 5 Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Kyoto, Japan. kakizuka@lif.kyoto-u.ac.jp.
PMID: 31395936 DOI: 10.1038/s41598-019-47993-w
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.

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