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j.heliyon.2016.e00096.pdf | 3.46 MB | Adobe PDF | 見る/開く |
タイトル: | Neuroprotective effects of VCP modulators in mouse models of glaucoma |
著者: | Nakano, Noriko Ikeda, Hanako Ohashi Hasegawa, Tomoko Muraoka, Yuki ![]() ![]() Iwai, Sachiko Tsuruyama, Tatsuaki ![]() Nakano, Masaki Fuchigami, Tomohiro Shudo, Toshiyuki Kakizuka, Akira ![]() ![]() Yoshimura, Nagahisa |
著者名の別形: | 池田, 華子 村岡, 勇貴 垣塚, 彰 吉村, 長久 |
キーワード: | Cell biology Neuroscience |
発行日: | Apr-2016 |
出版者: | Elsevier Ltd |
誌名: | Heliyon |
巻: | 2 |
号: | 4 |
論文番号: | e00096 |
抄録: | Glaucoma is a major cause of adult blindness due to gradual death of retinal ganglion cells. Currently, no therapeutics are available for the protection of these cells from the cell death. We have recently succeeded in synthesizing novel compounds, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption by specifically inhibiting the ATPase activities of VCP, a major ATPase in the cell, and we have shown that KUSs could mitigate the disease progression of rd10, a mouse model of retinitis pigmentosa, without any apparent side effects. Here we show that KUSs (e.g. KUS121 and KUS187) can prevent antimycin- and oligomycin-induced ATP depletion, endoplasmic reticulum (ER) stress, and cell death in neuronally differentiated PC12 cells. Furthermore, KUSs manifest significant efficacies on several mouse models of glaucoma. KUS administration prevented or mitigated ER stress and subsequent apoptotic cell death of retinal ganglion cells in an acute injury mouse model of retinal ganglion cell loss, which was induced with N-methyl-D-aspartate. In a mouse model of glaucoma with high intraocular pressure, KUSs prevented the typical glaucoma pathologies, i.e. enlargement of optic disc cupping and thinning of the retinal nerve fiber layer. KUSs also preserved visual functions in GLAST knockout mice, a mouse model for chronic retinal ganglion cell loss. We propose "ATP maintenance" via inhibition of ATPase activities of VCP as a promising new neuroprotective strategy for currently incurable eye diseases, such as glaucoma. |
記述: | 緑内障の進行を抑制、マウスで成功-新規の化合物を用いた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. 2016-04-22. |
著作権等: | © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/210500 |
DOI(出版社版): | 10.1016/j.heliyon.2016.e00096 |
PubMed ID: | 27441270 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2016-04-22 |
出現コレクション: | 学術雑誌掲載論文等 |
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