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-1α (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.
|Titolo:||Parkinson disease-associated DJ-1 is required for the expression of the glial cell line-derived neurotrophic factor receptor RET in human neuroblastoma cells|
|Autori:||FOTI R; ZUCCHELLI S; BIAGIOLI M; RONCAGLIA P; VILOTTI S; CALLIGARIS R; KRMAC H; GIRARDINI JE; DEL SAL G; GUSTINCICH S|
|Rivista:||THE JOURNAL OF BIOLOGICAL CHEMISTRY|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||10.1074/jbc.M109.088294|
|Appare nelle tipologie:||1.1 Journal article|