Neurotoxin-Induced Degeneration of Dopamine Neurons in Caenorhabditis elegans

Parkinson's disease is a complex neurodegenerative disorder characterized by the death of brain dopamine neurons. In mammals, dopamine neuronal degeneration can be triggered through exposure to neurotoxins accumulated by the presynaptic dopamine transporter (DAT), including 6-hydroxydopamine (6...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-03, Vol.99 (5), p.3264-3269
Main Authors: Nass, Richard, Hall, David H., Miller, David M., Blakely, Randy D.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological Sciences
Caenorhabditis elegans
Caenorhabditis elegans - drug effects
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - metabolism
Calcium-Binding Proteins - metabolism
Caspases - metabolism
Cell death
Cercopithecus aethiops
COS cells
COS Cells - metabolism
Dendrites
Dopamine - metabolism
Dopamine Plasma Membrane Transport Proteins
Helminth Proteins - metabolism
Medical genetics
Membrane Glycoproteins
Membrane Transport Proteins - genetics
Nematodes
Nerve Degeneration - chemically induced
Nerve Degeneration - metabolism
Nerve Tissue Proteins
Neuroglia
Neurons
Neurons - drug effects
Neurons - metabolism
Neurotoxins - metabolism
Neurotoxins - pharmacology
Oxidopamine - metabolism
Oxidopamine - pharmacology
Pharmacology
Toxins
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Summary:Parkinson's disease is a complex neurodegenerative disorder characterized by the death of brain dopamine neurons. In mammals, dopamine neuronal degeneration can be triggered through exposure to neurotoxins accumulated by the presynaptic dopamine transporter (DAT), including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium. We have established a system for the pharmacological and genetic evaluation of neurotoxin-induced dopamine neuronal death in Caenorhabditis elegans. Brief (1 h) exposure of green fluorescent protein-tagged, living worms to 6-OHDA causes selective degeneration of dopamine neurons. We demonstrate that agents that interfere with DAT function protect against 6-OHDA toxicity. 6-OHDA-triggered neural degeneration does not require the CED-3/CED-4 cell death pathway, but is abolished by the genetic disruption of the C. elegans DAT.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.042497999