中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (5): 815-816.doi: 10.4103/1673-5374.2

• 观点:退行性病与再生 • 上一篇    下一篇

DJ-1复合物和儿茶酚胺代谢的作用:家族性和特发性帕金森病的相关性

  

  • 收稿日期:2018-03-17 出版日期:2018-05-15 发布日期:2018-05-15

The role of DJ-1 complexes and catecholamine metabolism: relevance for familial and idiopathic Parkinson’s disease

Dominik Piston1, Matthew E. Gegg2   

  1. 1 German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany;
    2 Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK
  • Received:2018-03-17 Online:2018-05-15 Published:2018-05-15
  • Contact: Matthew E. Gegg, Ph.D.,matthew.gegg@ucl.ac.uk.
  • Supported by:

    This work was funded by a Medical Research Council (UK) Experimental Medicine grant [MR/M006646/1].

摘要:

orcid: 0000-0001-8093-0723 (Matthew E. Gegg)

Abstract:

Autosomal recessive mutations in the PARK7 gene, which encodes for the protein DJ-1, result in a loss of function and are a cause of familial Parkinson’s disease (PD), while increased wild-type DJ-1 protein levels are associated with some forms of cancer. Several functions of DJ-1 have been described, with the greatest evidence indicating that DJ-1 is a redox-sensitive protein involved in the regulation of oxidative stress and cell survival. We have recently reported that the levels of DJ-1 oxidized at cysteine 106 (C106) was decreased in the cortex of idiopathic PD brains (Piston et al., 2017). Furthermore we found that DJ-1 forms high molecular weight complexes in human brain and the dopaminergic SH-SY5Y neuroblastoma cell line, and that these complexes could be oxidized at C106. Proteomics indicated that proteins involved in RNA transcription/translation were associated with these DJ-1 complexes, and the composition of complexes was affected by oxidation of DJ-1. RNA sequencing highlighted that transcripts associated with the catecholamine system, including dopamine (DA) metabolism, tended to be increased when complexes contained DJ-1 mimicking oxidation at C106. DJ-1 knock down (KD) cells also had increased intracellular DA and noradrenaline (NA) levels. In this perspective we will discuss the implications of DJ-1 acting as a redox sensor directly affecting RNA metabolism, and with respect to PD, how dysregulation of catecholamine metabolism in both familial and idiopathic PD, might contribute to some prodromal features of the disease and the increased susceptibility of specific neuronal populations to neurodegeneration.DJ-1 complexes associated with RNA metabolism