PLoS ONE 2014-01-01

DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.

Mohammad Parsanejad, Noam Bourquard, Dianbo Qu, Yi Zhang, En Huang, Maxime W C Rousseaux, Hossein Aleyasin, Isabella Irrcher, Steve Callaghan, Dominique C Vaillant, Raymond H Kim, Ruth S Slack, Tak W Mak, Srinivasa T Reddy, Daniel Figeys, David S Park

Index: PLoS ONE 9(9) , e106601, (2014)

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Abstract

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2.