| Autor: |
Foti R; Sector of Neurobiology, International School for Advanced Studies, Giovanni Armenise-Harvard Foundation Laboratory, AREA Science Park, SS 14, Km 163.5, Basovizza, Italy., Zucchelli S, Biagioli M, Roncaglia P, Vilotti S, Calligaris R, Krmac H, Girardini JE, Del Sal G, Gustincich S |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2010 Jun 11; Vol. 285 (24), pp. 18565-74. Date of Electronic Publication: 2010 Apr 15. |
| DOI: |
10.1074/jbc.M109.088294 |
| Abstrakt: |
Mutations in PARK7/DJ-1 are associated with autosomal recessive, early onset Parkinson disease (PD). DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. Here we show that DJ-1 plays an essential role in the expression of rearranged during transfection (RET), a receptor for the glial cell line-derived neurotrophic factor, a neuroprotective molecule for dopaminergic neurons, the main target of degeneration in PD. The inducible loss of DJ-1 triggers the establishment of hypoxia and the production of reactive oxygen species that stabilize the hypoxia-inducible factor-1alpha (HIF-1a). HIF-1a expression is required for RET down-regulation. This study establishes for the first time a molecular link between the lack of functional DJ-1 and the glial cell line-derived neurotrophic factor signaling pathway that may explain the adult-onset loss of dopaminergic neurons. Furthermore, it suggests that hypoxia may play an important role in PD. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
