• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >The JAK/STAT3 Pathway Is a Common Inducer of Astrocyte Reactivity in Alzheimer's and Huntington's Diseases.
【2h】

The JAK/STAT3 Pathway Is a Common Inducer of Astrocyte Reactivity in Alzheimer's and Huntington's Diseases.

机译：JAK / STAT3途径是阿尔茨海默氏病和亨廷顿氏病中星形胶质细胞反应性的常见诱因。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Astrocyte reactivity is a hallmark of neurodegenerative diseases (ND), but its effects on disease outcomes remain highly debated. Elucidation of the signaling cascades inducing reactivity in astrocytes during ND would help characterize the function of these cells and identify novel molecular targets to modulate disease progression. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is associated with reactive astrocytes in models of acute injury, but it is unknown whether this pathway is directly responsible for astrocyte reactivity in progressive pathological conditions such as ND. In this study, we examined whether the JAK/STAT3 pathway promotes astrocyte reactivity in several animal models of ND. The JAK/STAT3 pathway was activated in reactive astrocytes in two transgenic mouse models of Alzheimer's disease and in a mouse and a nonhuman primate lentiviral vector-based model of Huntington's disease (HD). To determine whether this cascade was instrumental for astrocyte reactivity, we used a lentiviral vector that specifically targets astrocytes in vivo to overexpress the endogenous inhibitor of the JAK/STAT3 pathway [suppressor of cytokine signaling 3 (SOCS3)]. SOCS3 significantly inhibited this pathway in astrocytes, prevented astrocyte reactivity, and decreased microglial activation in models of both diseases. Inhibition of the JAK/STAT3 pathway within reactive astrocytes also increased the number of huntingtin aggregates, a neuropathological hallmark of HD, but did not influence neuronal death. Our data demonstrate that the JAK/STAT3 pathway is a common mediator of astrocyte reactivity that is highly conserved between disease states, species, and brain regions. This universal signaling cascade represents a potent target to study the role of reactive astrocytes in ND.
机译：星形胶质细胞反应性是神经退行性疾病（ND）的标志，但其对疾病结果的影响仍存在争议。阐明ND期间诱导星形胶质细胞反应性的信号级联反应将有助于表征这些细胞的功能并鉴定新的分子靶标以调节疾病进程。在急性损伤模型中，Janus激酶/信号转导子和转录激活因子3（JAK / STAT3）与反应性星形胶质细胞相关，但尚不清楚该通路是否直接导致进展性病理状况（例如ND）中的星形胶质细胞反应性。在这项研究中，我们检查了JAK / STAT3途径是否在几种ND动物模型中促进星形胶质细胞反应性。在两个阿尔茨海默氏病转基因小鼠模型以及基于亨廷顿氏病（HD）的小鼠和非人类灵长类慢病毒载体模型中，在反应性星形胶质细胞中激活了JAK / STAT3途径。为了确定该级联反应是否对星形胶质细胞反应起作用，我们使用了慢病毒载体，该载体在体内特异性靶向星形胶质细胞以过表达JAK / STAT3途径的内源性抑制剂[细胞因子信号传导抑制剂3（SOCS3）]。在这两种疾病的模型中，SOCS3均显着抑制星形胶质细胞中的该途径，阻止了星形胶质细胞的反应性并降低了小胶质细胞的活化。反应性星形胶质细胞内JAK / STAT3途径的抑制也增加了亨廷顿聚集体的数量，亨廷顿聚集体是HD的神经病理学标志，但不影响神经元死亡。我们的数据表明，JAK / STAT3途径是星形胶质细胞反应性的常见介体，在疾病状态，物种和大脑区域之间高度保守。这种通用的信号级联反应是研究反应性星形胶质细胞在ND中的作用的有效靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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