Parkinson disease-associated DJ-1 is required for the expression of the glial cell line-derived neurotrophic factor receptor RET in human neuroblastoma cells

Rossana Foti, Silvia Zucchelli, Marta Biagioli, Paola Roncaglia, Sandra Vilotti, Raffaella Calligaris, Helena Krmac, Javier Enrique Girardini, Giannino Del Sal, Stefano Gustincich

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

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.

Lingua originaleInglese
pagine (da-a)18565-18574
Numero di pagine10
RivistaJournal of Biological Chemistry
Volume285
Numero di pubblicazione24
DOI
Stato di pubblicazionePubblicato - 11 giu 2010
Pubblicato esternamente

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