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論文
- タイトル
- 視神経変性疾患の病態解明と治療研究
- タイトル（英）
- [Elucidation of the pathogenesis of optic nerve diseases and new therapeutic strategies to protect visual function].
- 参照URL
- https://researchmap.jp/takayukiharada/published_papers/51479127
- 著者
- 原田知加子,行方和彦,Guo Xiaoli,原田高幸
- 著者（英）
- Chikako Harada,Kazuhiko Namekata,Xiaoli Guo,Takayuki Harada
- 担当区分
- 概要
- 概要（英）
- Approximately 80% of all the information we receive about the world comes through the visual pathways and visual function deterioration causes severe decline in QOL. Glaucoma is the leading cause of blindness in the world, in which visual field deficit deteriorates as the optic nerve degeneration progresses. Hence, the development of fundamental cure is needed. Our research focuses on the signaling of brain-derived neurotrophic factor (BDNF), one neurotrophic factor reduced with aging and glaucoma patients. We generated modified tropomyosin receptor kinase B (TrkB) which can be constitutively activated in the absence of its ligand BDNF. The active site of TrkB is localized to the plasma membrane, allowing for constitutive activation of intracellular signaling. Gene therapy with the modified TrkB in a mouse model of glaucoma was proven to be protective. In addition, our group reported that apoptosis signal-regulating kinase 1 (ASK1), one of the stress response factors, is related to the severity of optic neuritis and myelitis in model mice of multiple sclerosis. We generated four lines of cell type specific ASK1 conditional knockout mice and found that ASK1 in glial cells increased the severity of neuroinflammation while ASK1 deficiency in immune cells had no significant effects. Further, we found that ASK1 is required in microglia and astrocytes to cause and maintain neuroinflammation by a feedback loop between these two cell types. Our results suggest that ASK1 might be a promising therapeutic target for reducing neuroinflammation including optic neuritis.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 日本薬理学雑誌
- 誌名（英）
- Nihon yakurigaku zasshi. Folia pharmacologica Japonica
- 巻
- 160
- 号
- 2
- 開始ページ
- 68
- 終了ページ
- 72
- 出版年月
- 2025年
- 査読の有無
- 招待の有無
- 掲載種別
- ISSN
- 0015-5691
- DOI URL
- https://doi.org/10.1254/fpj.24049
- 共同研究・競争的資金等の研究課題