Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a <it>Drosophila </it>model of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the most common movement disorder. Extrapyramidal motor symptoms stem from the degeneration of the dopaminergic pathways in patient brain. Current treatments for PD are symptomatic, alleviating diseas...

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Bibliographic Details
Main Authors: Yang Yufeng, Gehrke Stephan, Faust Katharina, Yang Lichuan, Beal M Flint, Lu Bingwei
Format: Article
Language:English
Published: BMC 2009-09-01
Series:BMC Neuroscience
Online Access:http://www.biomedcentral.com/1471-2202/10/109
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Summary:<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the most common movement disorder. Extrapyramidal motor symptoms stem from the degeneration of the dopaminergic pathways in patient brain. Current treatments for PD are symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Although the cause of PD remains unknown, several pathogenic factors have been identified, which cause dopaminergic neuron (DN) death in the substantia nigra (SN). These include oxidative stress, mitochondrial dysfunction, inflammation and excitotoxicity. Manipulation of these factors may allow the development of disease-modifying treatment strategies to slow neuronal death. Inhibition of DJ-1A, the <it>Drosophila </it>homologue of the familial PD gene DJ-1, leads to oxidative stress, mitochondrial dysfunction, and DN loss, making fly DJ-1A model an excellent <it>in vivo </it>system to test for compounds with therapeutic potential.</p> <p>Results</p> <p>In the present study, a <it>Drosophila </it>DJ-1A model of PD was used to test potential neuroprotective drugs. The drugs applied are the Chinese herb celastrol, the antibiotic minocycline, the bioenergetic amine coenzyme Q10 (coQ10), and the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo[f]-quinoxaline (NBQX). All of these drugs target pathogenic processes implicated in PD, thus constitute mechanism-based treatment strategies. We show that celastrol and minocycline, both having antioxidant and anti-inflammatory properties, confer potent dopaminergic neuroprotection in <it>Drosophila </it>DJ-1A model, while coQ10 shows no protective effect. NBQX exerts differential effects on cell survival and brain dopamine content: it protects against DN loss but fails to restore brain dopamine level.</p> <p>Conclusion</p> <p>The present study further validates <it>Drosophila </it>as a valuable model for preclinical testing of drugs with therapeutic potential for neurodegenerative diseases. The lower cost and amenability to high throughput testing make <it>Drosophila </it>PD models effective <it>in vivo </it>tools for screening novel therapeutic compounds. If our findings can be further validated in mammalian PD models, they would implicate drugs combining antioxidant and anti-inflammatory properties as strong therapeutic candidates for mechanism-based PD treatment.</p>
ISSN:1471-2202