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| Citation | Aron, L., Klein, P., Pham, T.T., Kramer, E.R., Wurst, W., Klein, R. (2010). Pro-Survival Role for Parkinson's Associated Gene DJ-1 Revealed in Trophically Impaired Dopaminergic Neurons. PLoS Biol. 8(4): e1000349. (Export to RIS) | ||
| FlyBase ID | FBrf0210541 | ||
| Publication Type | Research paper | ||
| PubMed ID | 20386724 | ||
| PubMed Abstract | The mechanisms underlying the selective death of substantia nigra (SN) neurons in Parkinson disease (PD) remain elusive. While inactivation of DJ-1, an oxidative stress suppressor, causes PD, animal models lacking DJ-1 show no overt dopaminergic (DA) neuron degeneration in the SN. Here, we show that aging mice lacking DJ-1 and the GDNF-receptor Ret in the DA system display an accelerated loss of SN cell bodies, but not axons, compared to mice that only lack Ret signaling. The survival requirement for DJ-1 is specific for the GIRK2-positive subpopulation in the SN which projects exclusively to the striatum and is more vulnerable in PD. Using Drosophila genetics, we show that constitutively active Ret and associated Ras/ERK, but not PI3K/Akt, signaling components interact genetically with DJ-1. Double loss-of-function experiments indicate that DJ-1 interacts with ERK signaling to control eye and wing development. Our study uncovers a conserved interaction between DJ-1 and Ret-mediated signaling and a novel cell survival role for DJ-1 in the mouse. A better understanding of the molecular connections between trophic signaling, cellular stress and aging could uncover new targets for drug development in PD. | ||
| DOI | 10.1371/journal.pbio.1000349 | ||
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| Language of Publication | English | ||
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| Publication Type | Journal | ||
| Abbreviation | PLoS Biol. | ||
| Title | PLoS Biology | ||
| Publication Year | 2003- | ||
| ISBN/ISSN | 1545-7885 1544-9173 | ||
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Data from Reference
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| Genes (6)
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