Drosophila mth mutant resists paraquat induced Parkinson’s like symptoms. Arvind K. Shukla^1*, Prakash Pragya¹, M.Z. Abdin², Debapratim Kar Chowdhuri¹. 1) Embryotoxicology, Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; 2) Department of Biotechnology, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062.

   Parkinsons disease (PD) is the second most common neurodegenerative disorder which involves degeneration of dopaminergic neurons. A well-known herbicide, paraquat (PQ), has been considered as one of the important risk factor for PD. Considering the well-characterized association between PQ and PD occurrence, there is a need for amelioration of PQ toxicity against PD. In recent years, the application of G protein coupled receptor (GPCR) in neurodegeneration has been suggested. Earlier, one of the important GPCRs in Drosophila, methuselah (mth), has been shown to provide increased survival to the organism against dietary PQ. Thus, the present study was aimed to examine the role of mth against PQ induced PD like symptoms using Drosophila as a model organism. Significant resistivity of mth mutant (mth1) flies against PQ induced oxidative stress in comparison to its parental control w1118 was observed. Marked deterioration in locomotor performance, degeneration of dopaminergic neurons along with decrease in dopamine (DA) pool was observed in PQ exposed w1118 flies while resistance towards all the above observed parameters was observed in mth1 flies. In contrast, flies that overexpress mth in their dopaminergic neurons when exposed to PQ exhibited more susceptibility to oxidative stress, behavioral deficit as well as increased neuronal death. The study demonstrated that mth mutation benefits the organism from PQ induced PD like symptoms which strengthens the possible role of GPCR in neurodegenerative disorder.