Targeted upregulation of dMyc restricts JNK-mediated degeneration of dopaminergic neurons in the paraquat-induced Parkinson's disease model of Drosophila.

Parkinson's disease is the second most common neurodegenerative disease characterized by the loss of dopaminergic neurons in the brain. Parkinson's disease has both familial and sporadic cases of origin governed differentially by genetic and/or environmental factors. Different epidemiological studies have proposed an association between the pathogenesis of cancer and Parkinson's disease; however, a precise correlation between these two illnesses could not be established yet. In this study, we examined the disease-modifying property of dmyc (a Drosophila homolog of human cmyc proto-oncogene) in the paraquat-induced sporadic Parkinson's disease model of Drosophila. We report for the first time that targeted upregulation of dMyc significantly restricts paraquat-mediated neurotoxicity. We observed that paraquat feeding reduces the cellular level of dMyc. We further noted that targeted upregulation of dMyc in paraquat-exposed flies mitigates degeneration of dopaminergic neurons by reinstating the aberrantly activated JNK pathway, and this in turn improves the motor performance and survival rate of the flies. Our study provides the first evidence that improved cellular level of dMyc could efficiently minimize the neurotoxic effects of paraquat, which could be beneficial in designing novel therapeutic strategies against Parkinson's disease. • Paraquat exposure reduces the cellular level of dMyc in Drosophila. • Upregulation of dMyc restricts paraquat-mediated degeneration of dopaminergic neurons in Drosophila. • Upregulation of dMyc improves motor performance and survival of paraquat exposed flies. • Upregulation of dMyc reinstates aberrantly activated JNK pathway to mitigate paraquat-mediated neurotoxicity. [ABSTRACT FROM AUTHOR]