• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Neuroscience >Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes caused by expression of mutant huntingtin protein in striatal neurons
【24h】

Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes caused by expression of mutant huntingtin protein in striatal neurons

机译：三环吡喃酮化合物可防止由纹状体神经元中突变的亨廷顿蛋白表达引起的聚集和细胞表型反转

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion mutation in the coding region of a novel gene. The mechanism of HD is unknown. Most data suggest that polyglutamine-mediated aggregation associated with expression of mutant huntingtin protein (mhtt) contributes to the pathology. However, recent studies have identified early cellular dysfunctions that preclude aggregate formation. Suppression of aggregation is accepted as one of the markers of successful therapeutic approaches. Previously, we demonstrated that tricyclic pyrone (TP) compounds efficiently inhibited formation of amyloid-β (Aβ) aggregates in cell and mouse models representing Alzheimer's Disease (AD). In the present study, we aimed to determine whether TP compounds could prevent aggregation and restore early cellular defects in primary embryonic striatal neurons from animal model representing HD. Results TP compounds effectively inhibit aggregation caused by mhtt in neurons and glial cells. Treatment with TP compounds also alleviated cholesterol accumulation and restored clathrin-independent endocytosis in HD neurons. Conclusion We have found that TP compounds not only blocked mhtt-induced aggregation, but also alleviated early cellular dysfunctions that preclude aggregate formation. Our data suggest TP molecules may be used as lead compounds for prevention or treatment of multiple neurodegenerative diseases including HD and AD.
机译：背景亨廷顿舞蹈病（HD）是一种由新基因编码区中的CAG重复扩增突变引起的进行性神经退行性疾病。 HD的机制尚不清楚。大多数数据表明，与谷胱甘肽突变体亨廷顿蛋白（mhtt）的表达有关的聚谷氨酰胺介导的聚集有助于病理。但是，最近的研究已经确定了早期的细胞功能障碍，可以阻止聚集体形成。抑制聚集被认为是成功治疗方法的标志之一。以前，我们证明三环吡喃酮（TP）化合物可有效抑制代表阿尔茨海默氏病（AD）的细胞和小鼠模型中淀粉样β（Aβ）聚集体的形成。在本研究中，我们旨在确定TP化合物是否可以从代表HD的动物模型中阻止聚集并恢复初级胚胎纹状体神经元的早期细胞缺陷。结果TP化合物有效抑制神经细胞和神经胶质细胞中由mhtt引起的聚集。 TP化合物的治疗还减轻了胆固醇的积累，并恢复了HD神经元中与网格蛋白无关的内吞作用。结论我们发现TP化合物不仅阻断了mhtt诱导的聚集，而且减轻了早期的细胞功能障碍，阻止了聚集体的形成。我们的数据表明，TP分子可用作预防或治疗包括HD和AD在内的多种神经退行性疾病的先导化合物。

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