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Neurobiol Aging. 2014 Oct;35(10):2419.e1-2419.e16. doi: 10.1016/j.neurobiolaging.2014.04.008. Epub 2014 Apr 18.

Mutation in Drosophila methuselah resists paraquat induced Parkinson-like phenotypes.

Author information

  • 1Embryotoxicology 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.
  • 2Embryotoxicology 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.
  • 3Analytical Section and Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India.
  • 4Department of Biotechnology, Jamia Hamdard, New Delhi, India.
  • 5Embryotoxicology Section and Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India. Electronic address: dkchowdhuri@iitr.res.in.

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Drosophila; Neurodegeneration; Paraquat; Parkinson's disease; mth

PMID:
24819147
[PubMed - indexed for MEDLINE]
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