| 16139214 |
Menzies FM, Yenisetti SC, Min KT: Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr Biol. 2005 Sep 6;15(17):1578-82.
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-1alpha and DJ-1beta. We found that DJ-1alpha is expressed predominantly in the testis, while DJ-1beta is ubiquitously present in most tissues, resembling the expression pattern of human DJ-1. Loss-of-function DJ-1beta 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-1alpha expression in the brain of the DJ-1beta mutant and demonstrated that overexpression of DJ-1alpha 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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