Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress
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- Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress
- Menzies, FM; Yenisetti, SC; Min, Kyung-Tai
- PARKINSONS-DISEASE; MODEL
- Issue Date
- CELL PRESS
- CURRENT BIOLOGY, v.15, no.17, pp.1578 - 1582
- The loss of dopaminergic neurons in the substantia nigra is the pathological hallmark of Parkinson's disease (PD). While the etiology of sporadic PD remains elusive, an inherited form of early-onset familial PD is linked to mutations of DJ-1 . To understand the biological function of DJ-1 and its relevance to the pathogenesis of PD, we investigated the function of DJ-1 using Drosophila. Drosophila possesses two homologs of human DJ-1: DJ-1 alpha and DJ-1 beta. We found that DJ-1a is expressed predominantly in the testis, while DJ-1 beta is ubiquitously present in most tissues, resembling the expression pattern of human DJ-1. Loss-of-function DJ-1 beta mutants demonstrated an extended survival of dopaminergic neurons and resistance to paraquat stress, but showed acute sensitivity to hydrogen peroxide treatment. We showed a compensatory upregulation of DJ-1 alpha expression in the brain of the DJ-1 beta mutant and demonstrated that overexpression of DJ-1 alpha in dopaminergic neurons is sufficient to confer protection against paraquat insult. These results suggest that Drosophila homologs of DJ-1 play critical roles in the survival of dopaminergic neurons and response to oxidative stress.
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