Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans

Richard Nass, David H. Hall, David M. Miller, Randy D. Blakely

Research output: Contribution to journalArticle

248 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)3264-3269
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number5
DOIs
StatePublished - Mar 5 2002

Keywords

  • Apoptosis
  • Catecholamine
  • Genetics
  • Parkinson's disease
  • Transporter

ASJC Scopus subject areas

  • General

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