...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis
【24h】

Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis

机译：氨基丙基咔唑在肌萎缩性侧索硬化小鼠模型中的神经保护作用

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

We previously reported the discovery of P7C3, an aminopropyl carbazole having proneurogenic and neuroprotective properties in newborn neural precursor cells of the hippocampal dentate gyrus. We have further found that chemicals having efficacy in this in vivo screening assay also protect dopaminergic neurons of the substantia nigra following exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a mouse model of Parkinson disease. Here, we provide evidence that an active analog of P7C3, known as P7C3A20, protects ventral horn spinal cord motor neurons from cell death in the G93A-SOD1 mutant mouse model of amyotrophic lateral sclerosis (ALS). P7C3A20 is efficacious in this model when administered at disease onset, and protection from cell death correlates with preservation of motor function in assays of walking gait and in the accelerating rotarod test. The prototypical member of this series, P7C3, delays disease progression in G93A-SOD1 mice when administration is initiated substantially earlier than the expected time of symptom onset. Dimebon, an antihistaminergic drug with significantly weaker proneurogenic and neuroprotective efficacy than P7C3, confers no protection in this ALS model. We propose that the chemical scaffold represented by P7C3 and P7C3A20 may provide a basis for the discovery and optimization of pharmacologic agents for the treatment of ALS.
机译：我们先前报道了在海马齿状回的新生神经前体细胞中具有促神经发生和神经保护特性的氨基丙基咔唑P7C3的发现。我们进一步发现，在暴露于神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（帕金森症的小鼠模型）后，在这种体内筛选试验中具有功效的化学物质还可以保护黑质的多巴胺能神经元。疾病。在这里，我们提供的证据表明，在肌萎缩性侧索硬化症（ALS）的G93A-SOD1突变小鼠模型中，P7C3的活性类似物称为P7C3A20，可以保护腹角脊髓运动神经元免受细胞死亡。 P7C3A20在疾病发作时在该模型中有效，在步行步态测定和加速旋转试验中，防止细胞死亡与运动功能的保持相关。当开始给药的时间比预期的症状发作时间早得多时，该系列的原型成员P7C3会延迟G93A-SOD1小鼠的疾病进展。 Dimebon是一种抗组织胺能药物，其促神经生成和神经保护功效明显低于P7C3，在此ALS模型中没有任何保护作用。我们建议以P7C3和P7C3A20为代表的化学支架可以为发现和优化用于治疗ALS的药理学提供基础。

著录项

  • 来源
  • 作者

    Rachel Tesla; Hamilton Parker Wolf; Pin Xu; Jordan Drawbridge; Sandi Jo Estill; Paula Huntington; LaTisha McDaniel; Whitney Knobbe; Aaron Burket; Stephanie Tran; Ruth Starwalt; Lorraine Morlock; Jacinth Naidoo; Noelle S. Williams; Joseph M. Ready; Steven L. McKnight; Andrew A. Pieper;

  • 作者单位

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;

    Departments of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390,Departments of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390,Department of Psychiatry, University of Iowa Carver College of Medi-cine, Iowa City, IA 52242;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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