CGC Bibliography Paper 5147

Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans.

Nass R, Hall DH, Miller DM, Blakely RD

Medline:

11867711

Citation:

Proceedings of the National Academy of Sciences USA 99: 3264-3269 2002

Type:

ARTICLE

Genes:

ced-1 ced-3 ced-4 dat-1

Abstract:

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 (11 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.