title: Mutation in Drosophila methuselah resists paraquat induced Parkinson-like phenotypes.
abstract: Parkinson's disease (PD) is a prevalent and devastating neurodegenerative disorder having limited cure options and strong association with the loss of dopaminergic neurons in the substantia nigra region of the mid brain. Etiology of PD includes both genetic and environmental factors. Paraquat (PQ), a widely used herbicide, is known to be associated with pathogenesis of PD. We report that a mutation in Drosophila methuselah (mth(1)), which is associated with aging, has a role in preventing dopaminergic neuronal cell death in PQ-exposed organism. Exposed mth(1) flies exhibit significant resistance against PQ-induced Parkinson's phenotypes and behavior in terms of oxidative stress, dopaminergic neuronal degeneration, locomotor performance, dopamine content, phosphorylated JNK, pFOXO, Hid, and cleaved caspase-3 levels. Conversely, over-expression of mth in dopaminergic neurons makes the exposed organism more vulnerable to oxidative stress, neuronal cell death, and behavioral deficit. The study suggests that lesser activation of JNK-mediated apoptosis in dopaminergic neurons of exposed mth(1) flies protects the organism from PQ-induced damage, which may be causally linked to a common mechanism for PQ-induced neurodegeneration.
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India; Department of Biotechnology, Jamia Hamdard, New Delhi, India.
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Shukla
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India; Department of Biotechnology, Jamia Hamdard, New Delhi, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Pragya
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Hitesh S
authors.initials: HS
authors.lastname: Chaouhan
authors.affiliation: Analytical Section and Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India.
authors.forename: D K
authors.initials: DK
authors.lastname: Patel
authors.affiliation: Department of Biotechnology, Jamia Hamdard, New Delhi, India.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Abdin
authors.affiliation: Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India. Electronic address: dkchowdhuri@iitr.res.in.
authors.forename: Debapratim
authors.initials: D
authors.lastname: Kar Chowdhuri
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000473:pathology; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053209:Herbicide Resistance / Q000235:genetics*; D006540:Herbicides / Q000009:adverse effects*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D009043:Motor Activity; D009154:Mutation; D009410:Nerve Degeneration / Q000517:prevention & control; D009479:Neuropeptides / Q000378:metabolism; D018384:Oxidative Stress; D010269:Paraquat / Q000009:adverse effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000235:genetics* / Q000517:prevention & control*; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; C108880:HID protein, Drosophila; D006540:Herbicides; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled; C115381:mth protein, Drosophila; D048670:MAP Kinase Kinase 4; D053148:Caspase 3; D010269:Paraquat; D004298:Dopamine
keywords: Drosophila; Neurodegeneration; Paraquat; Parkinson's disease; mth