PARKINSON’S DISEASE-ASSOCIATED DJ-1 IS REQUIRED FOR THE EXPRESSION OF THE GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR RECEPTOR RET IN HUMAN NEUROBLASTOMA CELLS

FOTI R.; ZUCCHELLI S.; BIAGIOLI M.; RONCAGLIA P.; VILLOTI S.; CALLIGARIS R.; KRMAC H.; GIRARDINI J.E.; DEL SAL G.; GUSTINCHIC S.

JOURNAL OF BIOLOGICAL CHEMISTRY (ONLINE)

American Society for Biochemistry and Molecular Biology

Año: 2010

1083-351X

Mutations in PARK7/DJ-1 are associatedwith autosomal recessive, early-onsetParkinson’s disease (PD). DJ-1 is an atypicalperoxiredoxin-like peroxidase that may act asa redox-dependent chaperone and a regulatorof transcription.Here we show that DJ-1 plays an essentialrole in the expression of Rearranged duringTransfection (RET), a receptor for the Glialcell line-derived neurotrophic factor (GDNF),a neuroprotective molecule for dopaminergic(DA) neurons, the main target ofdegeneration in PD. The inducible loss of DJ-1 triggers the establishment of hypoxia andthe production of reactive oxygen species thatstabilize the Hypoxia-inducible factor-1 alpha(HIF-1a). HIF-1a expression is required forRET down-regulation.This study establishes for the first time amolecular link between the lack of functionalDJ-1 and the GDNF signalling pathway thatmay explain the adult-onset loss of DAneurons. Furthermore, it suggests thathypoxia may play an important role in PD.