| First Author | Aron L | Year | 2010 |
| Journal | PLoS Biol | Volume | 8 |
| Issue | 4 | Pages | e1000349 |
| PubMed ID | 20386724 | Mgi Jnum | J:159857 |
| Mgi Id | MGI:4452559 | Doi | 10.1371/journal.pbio.1000349 |
| Citation | Aron L, et al. (2010) Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS Biol 8(4):e1000349 |
| abstractText | 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. |
