ParkinsonCanadaV1, Main, Exploration, bibRecord, 002C03

parkin counteracts symptoms in a Drosophila model of Parkinson's disease

Identifieur interne : 002C03 ( Main/Exploration ); précédent : 002C02; suivant : 002C04

parkin counteracts symptoms in a Drosophila model of Parkinson's disease

Auteurs : Annika Fm Haywood [Canada] ; Brian E. Staveley [Canada]

Source :

BMC Neuroscience [ 1471-2202 ] ; 2004.

RBID : PMC:419346

English descriptors

KwdEn :
- Amino Acid Sequence, Animals, Animals, Genetically Modified, Behavior, Animal, Conserved Sequence (genetics), Disease Models, Animal, Dopamine (metabolism), Drosophila Proteins (biosynthesis), Drosophila Proteins (genetics), Drosophila Proteins (physiology), Drosophila melanogaster, Gene Transfer Techniques, Genetic Therapy, Humans, Molecular Sequence Data, Nerve Tissue Proteins (genetics), Nerve Tissue Proteins (metabolism), Neurons (metabolism), Parkinson Disease (complications), Parkinson Disease (genetics), Parkinson Disease (therapy), Retinal Degeneration (genetics), Retinal Degeneration (pathology), Retinal Degeneration (therapy), Sequence Homology, Amino Acid, Survival Rate, Synucleins, Ubiquitin-Protein Ligases, alpha-Synuclein.
MESH :
- chemical , biosynthesis : Drosophila Proteins.
- chemical , genetics : Drosophila Proteins, Nerve Tissue Proteins.
- chemical , metabolism : Dopamine, Nerve Tissue Proteins.
- complications : Parkinson Disease.
- genetics : Conserved Sequence, Parkinson Disease, Retinal Degeneration.
- metabolism : Neurons.
- pathology : Retinal Degeneration.
- chemical , physiology : Drosophila Proteins.
- therapy : Parkinson Disease, Retinal Degeneration.
- Amino Acid Sequence, Animals, Animals, Genetically Modified, Behavior, Animal, Disease Models, Animal, Drosophila melanogaster, Gene Transfer Techniques, Genetic Therapy, Humans, Molecular Sequence Data, Sequence Homology, Amino Acid, Survival Rate, Synucleins, Ubiquitin-Protein Ligases, alpha-Synuclein.

Abstract

Background

Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α-synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α-synuclein in Drosophila neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD.

Results

To investigate the role of parkin, we have generated transgenic Drosophila that conditionally express parkin under the control of the yeast UAS enhancer. While expression of parkin has little consequence, co-expression of parkin with α-synuclein in the dopaminergic neurons suppresses the α-synuclein-induced premature loss of climbing ability. In addition directed expression of parkin in the eye counteracts the α-synuclein-induced degeneration of the ommatidial array. These results show that parkin suppresses the PD-like symptoms observed in the α-synuclein-dependent Drosophila model of PD.

Conclusion

The highly conserved parkin E3 ubiquitin ligase can suppress the damaging effects of human α-synuclein. These results are consistent with a role for parkin in targeting α-synuclein to the proteasome. If this relationship is conserved in humans, this suggests that up-regulation of parkin should suppress α-synucleinopathic PD. The development of therapies that regulate parkin activity may be crucial in the treatment of PD.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC419346

DOI: 10.1186/1471-2202-5-14
PubMed: 15090075
PubMed Central: 419346

Affiliations:

Canada

Le document en format XML

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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α-<italic>synuclein </italic>
and <italic>parkin </italic>
genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α-<italic>synuclein </italic>
in <italic>Drosophila </italic>
neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD.</p>
</sec>
<sec><title>Results</title>
<p>To investigate the role of <italic>parkin</italic>
, we have generated transgenic <italic>Drosophila </italic>
that conditionally express <italic>parkin </italic>
under the control of the yeast UAS enhancer. While expression of <italic>parkin </italic>
has little consequence, co-expression of <italic>parkin </italic>
with α-<italic>synuclein </italic>
in the dopaminergic neurons suppresses the α-<italic>synuclein</italic>
-induced premature loss of climbing ability. In addition directed expression of <italic>parkin </italic>
in the eye counteracts the α-<italic>synuclein</italic>
-induced degeneration of the ommatidial array. These results show that parkin suppresses the PD-like symptoms observed in the α-<italic>synuclein</italic>
-dependent <italic>Drosophila </italic>
model of PD.</p>
</sec>
<sec><title>Conclusion</title>
<p>The highly conserved <italic>parkin </italic>
E3 ubiquitin ligase can suppress the damaging effects of human α-synuclein. These results are consistent with a role for parkin in targeting α-synuclein to the proteasome. If this relationship is conserved in humans, this suggests that up-regulation of <italic>parkin </italic>
should suppress α-synucleinopathic PD. The development of therapies that regulate parkin activity may be crucial in the treatment of PD.</p>
</sec>
</div>
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La maladie de Parkinson au Canada (serveur d'exploration)

parkin counteracts symptoms in a Drosophila model of Parkinson's disease

parkin counteracts symptoms in a Drosophila model of Parkinson's disease

Source :

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

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	La maladie de Parkinson au Canada (serveur d'exploration)
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