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dc.contributor.authorOhashi Ikeda, Hanakoen
dc.contributor.authorSasaoka, Norioen
dc.contributor.authorKoike, Masaakien
dc.contributor.authorNakano, Norikoen
dc.contributor.authorMuraoka, Yukien
dc.contributor.authorToda, Yoshinobuen
dc.contributor.authorFuchigami, Tomohiroen
dc.contributor.authorShudo, Toshiyukien
dc.contributor.authorIwata, Ayanaen
dc.contributor.authorHori, Seijien
dc.contributor.authorYoshimura, Nagahisaen
dc.contributor.authorKakizuka, Akiraen
dc.contributor.alternative池田, 華子ja
dc.contributor.alternative吉村, 長久ja
dc.contributor.alternative垣塚, 彰ja
dc.date.accessioned2014-08-08T04:26:57Z-
dc.date.available2014-08-08T04:26:57Z-
dc.date.issued2014-08-06-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/2433/189386-
dc.description新規神経保護剤により網膜色素変性の進行を抑制することに成功 -難治性眼疾患の進行抑制に期待-. 京都大学プレスリリース. 2014-08-6.ja
dc.description.abstractNeuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs did not significantly impair reported cellular functions of VCP but nonetheless suppressed the VCP-dependent decrease of cellular ATP levels. Moreover, KUSs, as well as exogenous ATP or ATP-producing compounds, e.g. methylpyruvate, suppressed endoplasmic reticulum stress, and demonstrably protected various types of cultured cells from death, including several types of retinal neuronal cells. We then examined their in vivo efficacies in rd10, a mouse model of retinitis pigmentosa. KUSs prevented photoreceptor cell death and preserved visual function. These results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in this pathological context, and point to a promising new neuroprotective strategy for currently incurable retinitis pigmentosa.en
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherNature Publishing Groupen
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission fromthe license holder in order to reproduce thematerial. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.subjectDrug discoveryen
dc.subjectCell deathen
dc.titleNovel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa.en
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleScientific reportsen
dc.identifier.volume4-
dc.relation.doi10.1038/srep05970-
dc.textversionpublisher-
dc.identifier.artnum5970-
dc.identifier.pmid25096051-
dc.relation.urlhttps://www.kyoto-u.ac.jp/ja/research-news/2014-08-06-
dcterms.accessRightsopen access-
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