PMID- 31395936
OWN - NLM
STAT- MEDLINE
DCOM- 20201113
LR  - 20210203
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Aug 8
TI  - KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via 
      preventing ATP depletion.
PG  - 11519
LID - 10.1038/s41598-019-47993-w [doi]
LID - 11519
AB  - 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.
FAU - Kinoshita, Hisanori
AU  - Kinoshita H
AD  - Department of Neurology, Kyoto University Graduate School of Medicine, 54 
      Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
FAU - Maki, Takakuni
AU  - Maki T
AD  - 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.
FAU - Yasuda, Ken
AU  - Yasuda K
AD  - Department of Neurology, Kyoto University Graduate School of Medicine, 54 
      Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
FAU - Kishida, Natsue
AU  - Kishida N
AD  - Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Sasaoka, Norio
AU  - Sasaoka N
AD  - Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, 
      Kyoto, Japan.
FAU - Takagi, Yasushi
AU  - Takagi Y
AD  - Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Kakizuka, Akira
AU  - Kakizuka A
AD  - Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, 
      Kyoto, Japan. kakizuka@lif.kyoto-u.ac.jp.
FAU - Takahashi, Ryosuke
AU  - Takahashi R
AD  - Department of Neurology, Kyoto University Graduate School of Medicine, 54 
      Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
LA  - eng
PT  - Journal Article
DEP - 20190808
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (KUS121)
RN  - 0 (Naphthalenes)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Pyridines)
RN  - 0 (Sulfonic Acids)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Brain Ischemia/*prevention & control
MH  - Disease Models, Animal
MH  - Endoplasmic Reticulum Stress/drug effects
MH  - Infarction, Middle Cerebral Artery
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Naphthalenes/*pharmacology/therapeutic use
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Pyridines/*pharmacology/therapeutic use
MH  - Reproducibility of Results
MH  - Stroke/*prevention & control
MH  - Sulfonic Acids/*pharmacology/therapeutic use
PMC - PMC6687885
COIS- In relation to this manuscript, Kyoto University applied for patents; T.M., H.K., 
      A.K. and R.T. were the inventors of the patents. A.K. is a stock ownership for 
      Kyoto Drug Discovery & Development Co., Ltd., a start-up company for the 
      development of VCP modulators. The other authors declare no competing interests.
EDAT- 2019/08/10 06:00
MHDA- 2020/11/18 06:00
PMCR- 2019/08/08
CRDT- 2019/08/10 06:00
PHST- 2019/01/23 00:00 [received]
PHST- 2019/07/19 00:00 [accepted]
PHST- 2019/08/10 06:00 [entrez]
PHST- 2019/08/10 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2019/08/08 00:00 [pmc-release]
AID - 10.1038/s41598-019-47993-w [pii]
AID - 47993 [pii]
AID - 10.1038/s41598-019-47993-w [doi]
PST - epublish
SO  - Sci Rep. 2019 Aug 8;9(1):11519. doi: 10.1038/s41598-019-47993-w.