The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds

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dc.contributor.authorInamdar, Arati A.
dc.contributor.authorChaudhuri, Anathbandhu
dc.contributor.authorO'Donnell, Janis
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherRutgers State University New Brunswick
dc.contributor.otherUniversity of Nebraska Medical Center
dc.date.accessioned2023-09-28T22:03:43Z
dc.date.available2023-09-28T22:03:43Z
dc.date.issued2012
dc.description.abstractEpidemiological studies link the herbicide paraquat to increased incidence of Parkinson's disease (PD). We previously reported that Drosophila exposed to paraquat recapitulate PD symptoms, including region-specific degeneration of dopaminergic neurons. Minocycline, a tetracycline derivative, exerts ameliorative effects in neurodegenerative disease models, including Drosophila. We investigated whether our environmental toxin-based PD model could contribute to an understanding of cellular and genetic mechanisms of minocycline action and whether we could assess potential interference with these drug effects in altered genetic backgrounds. Cofeeding of minocycline with paraquat prolonged survival, rescued mobility defects, blocked generation of reactive oxygen species, and extended dopaminergic neuron survival, as has been reported previously for a genetic model of PD in Drosophila. We then extended this study to identify potential interactions of minocycline with genes regulating dopamine homeostasis that might modify protection against paraquat and found that deficits in GTP cyclohydrolase adversely affect minocycline rescue. We further performed genetic studies to identify signaling pathways that are necessary for minocycline protection against paraquat toxicity and found that mutations in the Drosophila genes that encode c-Jun N-terminal kinase (JNK) and Akt/Protein kinase B block minocycline rescue.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationInamdar, A. A., Chaudhuri, A., & O’Donnell, J. (2012). The Protective Effect of Minocycline in a Paraquat-Induced Parkinson’s Disease Model inDrosophilais Modified in Altered Genetic Backgrounds. In Parkinson’s Disease (Vol. 2012, pp. 1–16). Hindawi Limited. https://doi.org/10.1155/2012/938528
dc.identifier.doi10.1155/2012/938528
dc.identifier.orcidhttps://orcid.org/0000-0003-4833-3077
dc.identifier.urihttps://ir.ua.edu/handle/123456789/12202
dc.languageEnglish
dc.language.isoen_US
dc.publisherHindawi
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectACTIVATED PROTEIN-KINASE
dc.subjectOXIDATIVE STRESS
dc.subjectTYROSINE-HYDROXYLASE
dc.subjectNITRIC-OXIDE
dc.subjectMOUSE MODEL
dc.subjectMICROGLIAL ACTIVATION
dc.subjectSIGNALING PATHWAYS
dc.subjectMELANOGASTER
dc.subjectEXPRESSION
dc.subjectJNK
dc.subjectClinical Neurology
dc.titleThe Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgroundsen_US
dc.typeArticle
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