...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >mTORC1 signaling in Parkinson's disease and L-DOPA-induced dyskinesia: A sensitized matter.
【24h】

mTORC1 signaling in Parkinson's disease and L-DOPA-induced dyskinesia: A sensitized matter.

机译：帕金森氏病和L-DOPA诱发的运动障碍中的mTORC1信号传导：致敏物质。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Parkinson disease is caused by the progressive loss of dopamine innervation to the basal ganglia and is commonly treated with the dopamine precursor, L-DOPA. Prolonged administration of L-DOPA results in the development of severe motor complications or dyskinesia, which seriously hamper its clinical use. Recent evidence indicates that L-DOPA-induced dyskinesia (LID) is associated with persistent activation of the mammalian target of rapamycin complex 1 (mTORC1) in the medium spiny neurons (MSNs) of the striatum, the main component of the basal ganglia. This phenomenon is secondary to the development of a strong sensitization at the level of dopamine D1 receptors, which are abundantly expressed in a subset of MSNs. Such sensitization confers to dopaminergic drugs (including L-DOPA) the ability to activate the extracellular signal-regulated protein kinases 1/2, which, in turn promote mTORC1 signaling. Using a mouse model of LID, we recently showed that administration of the allosteric mTORC1 inhibitor, rapamycin, reduces dyskinesia. This finding is discussed with respect to underlying mechanisms and potential significance for the development of future therapeutic interventions.
机译：帕金森氏病是由多巴胺神经支配性逐渐丧失至基底神经节引起的，通常用多巴胺前体L-DOPA治疗。长期服用L-DOPA会导致严重的运动并发症或运动障碍，严重阻碍其临床应用。最近的证据表明，L-DOPA诱导的运动障碍（LID）与纹状体（基底神经节的主要成分）的中棘状神经元（MSNs）中雷帕霉素复合物1（mTORC1）的哺乳动物靶标的持续活化有关。这种现象是继多巴胺D1受体水平上的强敏化发展之后产生的，多巴胺D1受体在MSN的子集中大量表达。这种敏化作用赋予多巴胺能药物（包括L-DOPA）激活细胞外信号调节蛋白激酶1/2的能力，进而促进mTORC1信号传导。使用LID的小鼠模型，我们最近显示了变构mTORC1抑制剂雷帕霉素的给药可减轻运动障碍。讨论了这一发现，涉及潜在的机制以及对未来治疗干预措施发展的潜在意义。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号