Experimental study on effect of Rho kinase inhibitors against neurological impairment by environmental toxins

Rho激酶抑制剂对抗环境毒素神经损伤的实验研究

• 批准号: 20590135
• 负责人: FUJIMURA Masatake
• 金额: $ 3万
• 依托单位: National Institute for Minamata Disease
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590135/
• 关键词: 中毒学; 環境毒; 神経機能障害; ローキナーゼ阻害薬; 環境; 再生医学; 脳神経疾患; 薬理学

We mainly show that inhibition of the Rho kinase pathway prevents MeHg-intoxication. 2 Rho kinase inhibitors, Fasudil and Y-27632, significantly protected against axonal degeneration and apoptotic cell death in cultured cortical neuron exposed to MeHg. Fasudil also prevented the neuronal degeneration in peripheral nerves and hind limb crossing sign in MeHg-intoxicated model rats. Furthermore, Rho kinase inhibitors were effective for axonal degeneration and cell death in cultured cortical neuron exposed to inorganic mercury or Rotenone as a candidate substance responsible for Parkinson disease.

我们的主要研究表明，抑制Rho激酶通路可以防止甲基汞中毒。2 Rho激酶抑制剂法舒地尔和Y-27632对甲基汞所致培养的皮质神经元轴突变性和细胞凋亡有明显的保护作用。法舒地尔还能预防甲基汞中毒模型大鼠周围神经和后肢交叉征神经元的变性。此外，Rho激酶抑制剂对暴露于无机汞或鱼藤酮作为帕金森病候选物质的培养的皮质神经元的轴突变性和细胞死亡有效。

项目成果

Signal transduction systems involved in methylmercury-cytotoxicity. (In : Aschner M and Ceccatelli S (ed.))

参与甲基汞细胞毒性的信号转导系统。

• 作者: Usuki F;Fujimura M
• 通讯作者: Fujimura M

Methylmercury exposure downregulates the expression of Racl and leads to neuritic degeneration and ultimately apoptosis in cerebrocortical neurons

• DOI: 10.1016/j.neuro.2008.10.002
• 发表时间: 2009-01-01
• 期刊: NEUROTOXICOLOGY
• 影响因子: 3.4
• 作者: Fujimura, Masatake;Usuki, Fusako;Takashima, Akihiko
• 通讯作者: Takashima, Akihiko

メチル水銀による大脳皮質神経細胞の細胞死機構

甲基汞导致大脑皮层神经元细胞死亡的机制

• 发表时间: 2008
• 作者: Shima k;Tanji J;藤村成剛
• 通讯作者: 藤村成剛

Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure

• DOI: 10.1016/j.taap.2010.09.011
• 发表时间: 2011-01-01
• 期刊: TOXICOLOGY AND APPLIED PHARMACOLOGY
• 影响因子: 3.8
• 作者: Fujimura, Masatake;Usuki, Fusako;Izumo, Shuji
• 通讯作者: Izumo, Shuji

Methylmercury exposure downregulates the expression of Racl, leads to neuritic degeneration and ultimately apoptosis in cerebrocortical neurons.

甲基汞暴露会下调 Racl 的表达，导致神经炎变性，最终导致大脑皮质神经元凋亡。

• 发表时间: 2009
• 期刊: Neurotoxicology 30
• 作者: Fujimura M;Usuki F;Sawada M;Rostene W;Godefroy D;Takashima A
• 通讯作者: Takashima A