Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans.

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  • Author(s): Nass R;Nass R; Hall DH; Miller DM 3rd; Blakely RD
  • Source:
    Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2002 Mar 05; Vol. 99 (5), pp. 3264-9. Date of Electronic Publication: 2002 Feb 26.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Membrane Glycoproteins* ; Nerve Tissue Proteins*; Dopamine/*metabolism ; Nerve Degeneration/*metabolism ; Neurons/*drug effects ; Neurotoxins/*pharmacology ; Oxidopamine/*pharmacology; Animals ; COS Cells/metabolism ; Caenorhabditis elegans/drug effects ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Calcium-Binding Proteins/metabolism ; Caspases/metabolism ; Chlorocebus aethiops ; Dopamine Plasma Membrane Transport Proteins ; Helminth Proteins/metabolism ; Membrane Transport Proteins/genetics ; Nerve Degeneration/chemically induced ; Neurons/metabolism ; Neurotoxins/metabolism ; Oxidopamine/metabolism
    • 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.
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    • Grant Information:
      R24 OD010943 United States OD NIH HHS; T32 MH019732 United States MH NIMH NIH HHS; R24 RR012596 United States RR NCRR NIH HHS; P30 DK020593 United States DK NIDDK NIH HHS; RR12596 United States RR NCRR NIH HHS; P01DK58212 United States DK NIDDK NIH HHS; CA68485 United States CA NCI NIH HHS; DK20593 United States DK NIDDK NIH HHS; P01 DK058212 United States DK NIDDK NIH HHS; P30 CA068485 United States CA NCI NIH HHS; MH19732-07 United States MH NIMH NIH HHS
    • Accession Number:
      0 (Caenorhabditis elegans Proteins)
      0 (Calcium-Binding Proteins)
      0 (Ced-4 protein, C elegans)
      0 (Dopamine Plasma Membrane Transport Proteins)
      0 (Helminth Proteins)
      0 (Membrane Glycoproteins)
      0 (Membrane Transport Proteins)
      0 (Nerve Tissue Proteins)
      0 (Neurotoxins)
      8HW4YBZ748 (Oxidopamine)
      EC 3.4.22.- (Caspases)
      EC 3.4.22.- (ced-3 protein, C elegans)
      VTD58H1Z2X (Dopamine)
    • Publication Date:
      Date Created: 20020228 Date Completed: 20020426 Latest Revision: 20221101
    • Publication Date:
      20221213
    • Accession Number:
      PMC122507
    • Accession Number:
      10.1073/pnas.042497999
    • Accession Number:
      11867711