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

Piston, D; Gegg, ME; (2018) The role of DJ-1 complexes and catecholamine metabolism: relevance for familial and idiopathic Parkinson's disease. Neural Regeneration Research , 13 (5) pp. 815-816. 10.4103/1673-5374.232474. Green open access

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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.

Type: Article
Title: The role of DJ-1 complexes and catecholamine metabolism: relevance for familial and idiopathic Parkinson's disease
Location: India
Open access status: An open access version is available from UCL Discovery
DOI: 10.4103/1673-5374.232474
Publisher version: http://dx.doi.org/10.4103/1673-5374.232474
Language: English
Additional information: This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/10050939
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