Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice.

Milnerwood AJ; Gladding CM; Pouladi MA; Kaufman AM; Hines RM; Boyd JD; Ko RW; Vasuta OC; Graham RK; Hayden MR; Murphy TH; Raymond LA

首页> 外文期刊>Neuron >Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice.

【24h】

Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice.

机译：突触外NMDA受体信号和表达的早期增加有助于亨廷顿舞蹈病小鼠的表型发作。

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

N-methyl-D-aspartate receptor (NMDAR) excitotoxicity is implicated in the pathogenesis of Huntington's disease (HD), a late-onset neurodegenerative disorder. However, NMDARs are poor therapeutic targets, due to their essential physiological role. Recent studies demonstrate that synaptic NMDAR transmission drives neuroprotective gene transcription, whereas extrasynaptic NMDAR activation promotes cell death. We report specifically increased extrasynaptic NMDAR expression, current, and associated reductions in nuclear CREB activation in HD mouse striatum. The changes are observed in the absence of dendritic morphological alterations, before and after phenotype onset, correlate with mutation severity, and require caspase-6 cleavage of mutant huntingtin. Moreover, pharmacological block of extrasynaptic NMDARs with memantine reversed signaling and motor learning deficits. Our data demonstrate elevated extrasynaptic NMDAR activity in an animal model of neurodegenerative disease. We provide a candidate mechanism linking several pathways previously implicated in HD pathogenesis and demonstrate successful early therapeutic intervention in mice.

机译：N-甲基-D-天冬氨酸受体（NMDAR）兴奋性毒性与亨廷顿舞蹈病（HD）的发病机理有关，后者是一种迟发性神经退行性疾病。但是，NMDAR由于其必不可少的生理作用，因此治疗效果较差。最近的研究表明，突触NMDAR传递驱动神经保护性基因转录，而突触外NMDAR激活则促进细胞死亡。我们报告特别增加突触外NMDAR表达，当前和相关的减少高清小鼠纹状体中核CREB激活。在表型发作之前和之后，在没有树突形态学改变的情况下观察到这些变化，其与突变的严重程度相关，并且需要突变型亨廷顿蛋白的caspase-6裂解。此外，与美金刚逆转信号和运动学习缺陷的突触外NMDARs的药理学障碍。我们的数据表明在神经退行性疾病的动物模型中突触外NMDAR活性升高。我们提供了一种候选机制，该机制链接了先前与高清发病机制有关的几种途径，并证明了在小鼠中成功的早期治疗干预。

著录项

来源
《Neuron》 |2010年第2期|共13页
作者
Milnerwood AJ; Gladding CM; Pouladi MA; Kaufman AM; Hines RM; Boyd JD; Ko RW; Vasuta OC; Graham RK; Hayden MR; Murphy TH; Raymond LA;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类神经生理学;
关键词

相似文献

外文文献
中文文献
专利

1. Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice. [J] . Milnerwood AJ, Gladding CM, Pouladi MA, Neuron . 2010,第2期

机译：突触外NMDA受体信号和表达的早期增加有助于亨廷顿舞蹈病小鼠的表型发作。
2. Calpain and STriatal-Enriched protein tyrosine Phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a huntington's disease mouse model [J] . GladdingC.M., SepersM.D., XuJ., Human Molecular Genetics . 2012,第17期

机译：钙蛋白酶和富含STRATAL的蛋白酪氨酸磷酸酶（STEP）的激活有助于亨廷顿病小鼠模型中突触外NMDA受体的定位
3. Calpain and STriatal-Enriched protein tyrosine Phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model [J] . Clare M. Gladding1 Marja D. Sepers1 Jian Xu2 Lily Y.J. Zhang1 Austen J. Milnerwood1 Paul J. Lombroso2 and Lynn A. Raymond1* Human Molecular Genetics . 2012,第17期

机译：钙蛋白酶和富含STRATAL的蛋白酪氨酸磷酸酶（STEP）的激活有助于亨廷顿舞蹈病小鼠模型中突触外NMDA受体的定位
4. Label Propagation Based Semi-supervised Feature Selection to Decode Clinical Phenotype of Huntington's Disease [C] . Xue Jiang, Miao Chen, Weidi Wang, International conference on intelligent computing . 2019

机译：基于标签传播的半监督特征选择解码亨廷顿病的临床表型
5. The role of extrasynaptic NMDA receptors in synaptic transmission and plasticity. [D] . Harris, Alexander Z. 2009

机译：突触外NMDA受体在突触传递和可塑性中的作用。
6. Calpain and STriatal-Enriched protein tyrosine Phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntingtons disease mouse model [O] . Clare M. Gladding, Marja D. Sepers, Jian Xu, -1

机译：钙蛋白酶和富含STRATAL的蛋白酪氨酸磷酸酶（STEP）的激活有助于亨廷顿舞蹈病小鼠模型中突触外NMDA受体的定位
7. Early Increase in Extrasynaptic NMDA Receptor Signaling and Expression Contributes to Phenotype Onset in Huntington's Disease Mice [O] . Milnerwood Austen J., Gladding Clare M., Pouladi Mahmoud A., 2010

机译：突触外NMDA受体信号和表达的早期增加有助于亨廷顿氏病小鼠的表型发作。

Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice.

摘要

著录项

相似文献

相关主题

期刊订阅