中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 69-70.doi: 10.4103/1673-5374.264459

• 观点:退行性病与再生 • 上一篇    下一篇

亨廷顿病中的兴奋性突触损伤和线粒体功能障碍:热休克因子1会聚机制

  

  • 出版日期:2020-01-15 发布日期:2020-05-15

Excitatory synapse impairment and mitochondrial dysfunction in Huntington’s disease: heat shock factor 1 (HSF1) converging mechanisms

Nicole Zarate, Rocio Gomez-Pastor   

  1. Department of Neuroscience, School of Medicine, University of Minnesota, Minneapolis, MN, USA
  • Online:2020-01-15 Published:2020-05-15
  • Contact: Rocio Gomez-Pastor, PhD,rgomezpa@umn.edu.

摘要: orcid: 0000-0003-1136-5462 (Rocio Gomez-Pastor)

Abstract: Heat shock factor 1 (HSF1) is abnormally degraded in Huntington’s disease (HD): HD is a neurodegenerative disorder characterized by severe cognitive and motor impairments. HD is caused by a CAG repeat expansion within exon 1 of the huntingtin (HTT) gene (The Huntington’s Disease Collaborative Research Group, 1993). These expansions lead to the production of an aberrant mutant huntingtin protein (mHTT) that is prone to misfolding and aggregation. Expression and aggregation of mHTT is present in virtually all cell types in the body but preferentially affects medium spiny neurons of the striatum, a brain region that controls movement and some forms of cognition. Accumulation of mHTT leads to, but not only, transcriptional dysregulation, DNA damage, mitochondrial dysfunction and excitatory synaptic failure ultimately causing neuronal death. However, the molecular mechanisms by which mHTT exerts these defects are still unclear.