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Parkinson Disease-associated DJ-1 Is Required for the Expression of the Glial Cell Line-derived Neurotrophic Factor Receptor RET in Human Neuroblastoma Cells*

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


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

Topics: Molecular Bases of Disease
Publisher: American Society for Biochemistry and Molecular Biology
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Provided by: PubMed Central
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