English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.

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