...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Neuroscience >parkin counteracts symptoms in a Drosophila model of Parkinson's disease
【24h】

parkin counteracts symptoms in a Drosophila model of Parkinson's disease

机译：帕金森对抗果蝇帕金森病模型中的症状

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

摘要

Background Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α- synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α- synuclein in Drosophila neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD. Results To investigate the role of parkin , we have generated transgenic Drosophila that conditionally express parkin under the control of the yeast UAS enhancer. While expression of parkin has little consequence, co-expression of parkin with α- synuclein in the dopaminergic neurons suppresses the α- synuclein -induced premature loss of climbing ability. In addition directed expression of parkin in the eye counteracts the α- synuclein -induced degeneration of the ommatidial array. These results show that parkin suppresses the PD-like symptoms observed in the α- synuclein -dependent Drosophila model of PD. Conclusion The highly conserved parkin E3 ubiquitin ligase can suppress the damaging effects of human α-synuclein. These results are consistent with a role for parkin in targeting α-synuclein to the proteasome. If this relationship is conserved in humans, this suggests that up-regulation of parkin should suppress α-synucleinopathic PD. The development of therapies that regulate parkin activity may be crucial in the treatment of PD.
机译：背景技术帕金森氏病是一种普遍的神经退行性疾病，其特征是多巴胺能神经元减少，从而导致运动控制丧失，静息震颤，神经元内含物形成并最终过早死亡。 PD的两种遗传形式已与α-突触核蛋白和帕金基因的突变相关。帕金蛋白起着针对特定蛋白质降解的泛素连接酶的作用。人α-突触核蛋白在果蝇神经元中的表达概括了运动控制的丧失，神经元内含物的发育，多巴胺能神经元的变性和ommatidial阵列，为PD提供了出色的遗传模型。结果为了研究Parkin的作用，我们产生了在酵母UAS增强子的控制下有条件表达Parkin的转基因果蝇。尽管Parkin的表达几乎没有影响，但在多巴胺能神经元中parkin与α-突触核蛋白的共表达抑制了α-突触核蛋白诱导的过早爬升能力。另外，在眼中Parkin的定向表达抵消了α-突触核蛋白诱导的卵母细胞阵列的变性。这些结果表明，帕金蛋白抑制在PD的α-突触核蛋白依赖性果蝇模型中观察到的PD样症状。结论高度保守的Parkin E3泛素连接酶可以抑制人α-突触核蛋白的破坏作用。这些结果与帕金在将α-突触核蛋白靶向蛋白酶体中的作用一致。如果在人类中保持这种关系，则表明帕金斯蛋白的上调应抑制α-突触核蛋白传递性PD。调节Parkin活性的疗法的发展对于PD的治疗可能至关重要。

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