中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (7): 1053-1054.doi: 10.4103/1673-5374.160077

• 观点:退行性病与再生 • 上一篇    下一篇

基因治疗帕金森病:确定的新目标?

  

  • 收稿日期:2015-05-11 出版日期:2015-07-24 发布日期:2015-07-24

Gene therapy in Parkinson’s disease: targeting the endplasmic reticulum proteostasis network

Valentina Castillo, Gabriela Mercado, Claudio Hetz   

  1. Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile (Castillo V, Mercado G, Hetz C)
    Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago, Chile (Castillo V, Mercado G, Hetz C)
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA (Hetz C)
  • Received:2015-05-11 Online:2015-07-24 Published:2015-07-24
  • Contact: Claudio Hetz, Ph.D. or Gabriela Mercado, Ph.D., chetz@hsph.harvard.edu or mariamercado@med.uchile.cl.
  • Supported by:

    This work is supported by FONDECYT-11140738 (G.M.). Michael J. Fox Foundation for Parkinson Research, Ring Initiative ACT1109, and FONDEF D11I1007 (C.H.). We also thank, FONDECYT-1140549, Millennium Institute P09-015-F, COPEC-UC, and Frick Foundation (C.H.). V.C. is supported by CONICYT fellowship.

摘要:

越来越多的证据表明,细胞器内稳态的扰动可能与神经退行性疾病的蛋白质错误折叠有关,包括帕金森病,阿尔茨海默病和肌萎缩性侧索硬化。最近的研究已经证明,活化的未折叠蛋白应答会发生在大多数帕金森病动物模型和人脑组织来源的帕金森病患者中。在分子水平上,体内ER应激中的突变alpha突触核蛋白积累、神经元功能障碍以及活化的未折叠蛋白应答之间存在紧密联系。虽然未折叠蛋白应答的组成部分已可在若干种神经退行性变疾病的情况下被操控,但我们对其在神经系统所述通路的可能生理功能仍然知之甚少。根据已公布的研究数据,我们预测内质网应激在不同神经退行性疾病中的影响是复杂的,因为它可以取决于涉及每种疾病的病理刺激性质。通过针对通路观察对比结果的特定信号成分,未折叠蛋白应答对帕金森病的影响已在最近数份研究报道中进行了测试。