The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds
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, ex...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2012/938528 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850109834400104448 |
|---|---|
| author | Arati A. Inamdar Anathbandhu Chaudhuri Janis O’Donnell |
| author_facet | Arati A. Inamdar Anathbandhu Chaudhuri Janis O’Donnell |
| author_sort | Arati A. Inamdar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-434860c5346544bdb614fa4673791ed9 |
| institution | OA Journals |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-434860c5346544bdb614fa4673791ed92025-08-20T02:37:58ZengWileyParkinson's Disease2090-80832042-00802012-01-01201210.1155/2012/938528938528The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic BackgroundsArati A. Inamdar0Anathbandhu Chaudhuri1Janis O’Donnell2Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487-0344, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487-0344, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487-0344, USAEpidemiological 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.http://dx.doi.org/10.1155/2012/938528 |
| spellingShingle | Arati A. Inamdar Anathbandhu Chaudhuri Janis O’Donnell The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds Parkinson's Disease |
| title | The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds |
| title_full | The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds |
| title_fullStr | The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds |
| title_full_unstemmed | The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds |
| title_short | The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds |
| title_sort | protective effect of minocycline in a paraquat induced parkinson s disease model in drosophila is modified in altered genetic backgrounds |
| url | http://dx.doi.org/10.1155/2012/938528 |
| work_keys_str_mv | AT aratiainamdar theprotectiveeffectofminocyclineinaparaquatinducedparkinsonsdiseasemodelindrosophilaismodifiedinalteredgeneticbackgrounds AT anathbandhuchaudhuri theprotectiveeffectofminocyclineinaparaquatinducedparkinsonsdiseasemodelindrosophilaismodifiedinalteredgeneticbackgrounds AT janisodonnell theprotectiveeffectofminocyclineinaparaquatinducedparkinsonsdiseasemodelindrosophilaismodifiedinalteredgeneticbackgrounds AT aratiainamdar protectiveeffectofminocyclineinaparaquatinducedparkinsonsdiseasemodelindrosophilaismodifiedinalteredgeneticbackgrounds AT anathbandhuchaudhuri protectiveeffectofminocyclineinaparaquatinducedparkinsonsdiseasemodelindrosophilaismodifiedinalteredgeneticbackgrounds AT janisodonnell protectiveeffectofminocyclineinaparaquatinducedparkinsonsdiseasemodelindrosophilaismodifiedinalteredgeneticbackgrounds |