![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
![[thumbnail of Original text]](https://edoc.mdc-berlin.de/style/images/fileicons/application_pdf.png) |
PDF (Original text)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
| Item Type: | Article |
|---|---|
| Title: | Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism |
| Creators Name: | Meiser, J., Delcambre, S., Wegner, A., Jaeger, C., Ghelfi, J., D'Herouel, A.F., Dong, X., Weindl, D., Stautner, C., Nonnenmacher, Y., Michelucci, A., Popp, O., Giesert, F., Schildknecht, S., Kraemer, L., Schneider, J.G., Woitalla, D., Wurst, W., Skupin, A., Weisenhorn, D.M.V., Krueger, R., Leist, M. and Hiller, K. |
| Abstract: | The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an important function in cellular antioxidant responses, but its role in central metabolism of neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect of a functional loss of DJ-1 and show that DJ-1 deficient neuronal cells exhibit decreased glutamine influx and reduced serine biosynthesis. By providing precursors for GSH synthesis, these two metabolic pathways are important contributors to cellular antioxidant response. Down-regulation of these pathways, as a result of loss of DJ-1 leads to an impaired antioxidant response. Furthermore, DJ-1 deficient mouse microglia showed a weak but constitutive pro-inflammatory activation. The combined effects of altered central metabolism and constitutive activation of glia cells raise the susceptibility of dopaminergic neurons towards degeneration in patients harboring mutated DJ-1. Our work reveals metabolic alterations leading to increased cellular instability and identifies potential new intervention points that can further be studied in the light of novel translational medicine approaches. |
| Keywords: | Parkinson's Disease, Mitochondrial Metabolism, Glutamine, Serine, Folate Mediated One-Carbon Metabolism, Oxidative Stress, ROS, Glutathione, Stable Isotope-Assisted Metabolomics, GC/MS, Animals, Mice |
| Source: | Neurobiology of Disease |
| ISSN: | 0969-9961 |
| Publisher: | Elsevier / Academic Press |
| Volume: | 89 |
| Page Range: | 112-125 |
| Date: | May 2016 |
| Additional Information: | Copyright © 2016 The Authors |
| Official Publication: | https://doi.org/10.1016/j.nbd.2016.01.019 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
