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Inamdar, A.A., Chaudhuri, A., O'Donnell, J. (2012). The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds.  Parkinsons Dis. 2012(): 938528.
FlyBase ID
FBrf0219235
Publication Type
Research paper
Abstract

Epidemiological 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.

PubMed ID
PubMed Central ID
PMC3413958 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Parkinsons Dis.
    Title
    Parkinson's disease
    ISBN/ISSN
    2042-0080 2090-8083
    Data From Reference
    Genes (8)
    Human Disease Models (1)