Analysis of Dock8 and ASK1 functions in optic nerve regeneration

• Project/Area Number: 24791884
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KITTAKA Daiji 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研究員 (50623782)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ASK1 / 視神経再生 / 炎症 / 国際情報交換

Research Abstract

Neurons are normally unable to regenerate their axons in the central nervous system, but neuroinflammation induced by a proinflammatory agent such as zymosan stimulates axonal regeneration. Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase kinase kinase (MAP3K) and plays important roles in neural cell death and inflammation. In the present study, we found that zymosan-stimulated optic nerve regeneration is severely suppressed in ASK1-deficient mice. ASK1 was required for the zymosan-stimulated migration of macrophages into the mouse retina, and oncomodulin production in macrophages and retinal Müller glia. However, ASK1 deficiency in retinal ganglion cells had no effect on axonal outgrowth. These results suggest that ASK1 signaling in non-neuronal cells plays important roles in zymosan-stimulated optic nerve regeneration.

Research Products

• [Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury (2013)
  • Author(s): Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T
  • Journal Title: Cell Death and Differentiation Volume: 20 Pages: 270-280
  • Peer Reviewed
• [Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury. (2013)
  • Author(s): Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T.
  • Journal Title: Cell Death Differ. Volume: 20 Issue: 2 Pages: 270-280
  • DOI: 10.1038/cdd.2012.122
  • Peer Reviewed
• [Journal Article] Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG (2012)
  • Author(s): Namekata K, Watanabe H, Guo X, Kittaka D, Kawamura K, Kimura A, Harada C, Harada T
  • Journal Title: Genes Cells Volume: 17(8) Pages: 688-97
  • Peer Reviewed
• [Journal Article] Dock3 stimulates axonal outgrowth via GSK-3β-mediated microtubule assembly (2012)
  • Author(s): Namekata K, Harada C, Guo X, Kimura H, Kittaka D, Watanabe H, and Harada T
  • Journal Title: Journal of Neuroscience Volume: 32(1) Pages: 264-274
  • Peer Reviewed
• [Journal Article] Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG. (2012)
  • Author(s): Namekata K、他6名
  • Journal Title: Genes to Cells. Volume: 17 Issue: 8 Pages: 688-697
  • DOI: 10.1111/j.1365-2443.2012.01616.x
  • Peer Reviewed
• [Presentation] Roles of ASK1 in neuroprotection and axonal regeneration after optic nerve injury (2013)
  • Author(s): Daiji Kittaka, Kazuhiko Namekata, Takuji Kurimoto, Xiaoli Guo, Chikako Harada, Takayuki Harada
  • Organizer: 43rd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2013-11-10
• [Presentation] Roles of ASK1 in neuroprotection and axonal regeneration after optic nerve injury.
  • Author(s): 橘高大二
  • Organizer: 43rd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Book] Dock3 はグリコーゲン合成酵素キナーゼ-3β (GSK-3β)による微小管重合を介して軸索伸長を促進する (2012)
  • Author(s): 行方和彦, 原田知加子, 郭 暁麗, 木村敦子, 橘高大二, 渡邉快記, 原田高幸
  • Total Pages: 527
  • Publisher: 日本眼科学会会誌
• [Remarks]
  • URL: http://www.igakuken.or.jp
• [Remarks] 視覚病態プロジェクトの研究紹介
  • URL: http://www.igakuken.or.jp/retina/