Caenorhabditis elegans MPP+ model of Parkinson's disease for high-throughput drug screenings.
The neurotoxin MPTP and its active metabolite MPP+ cause Parkinson's disease (PD)-like symptoms in vertebrates by selectively destroying dopaminergic neurons in the substantia nigra. MPTP/MPP+ models have been established in rodents to screen for pharmacologically active compounds. In addition to being costly and time consuming, these animal models are not suitable for large scale testings using compound libraries. We present a novel MPP+-based model for high-throughput screenings using the nematode Caenorhabditis elegans. Incubation of C. elegans with MPTP or its active metabolite MPP+ resulted in strong symptomatic defects including reduced mobility and increased lethality, and is correlated with a specific degeneration of the dopaminergic neurons. The phenotypic consequences of MPTP/MPP+ treatments were recorded using automated hardware and software for quantification. Incubation of C. elegans with a variety of pharmacologically active components used in PD treatment reduced the MPP+-induced defects. Our data suggest that the C. elegans MPTP/MPP+ model can be used for the quantitative evaluation of anti-PD drugs.
Braungart
Evelyn
E
Pieris Proteolab AG, Freising-Weihenstephan, Würzburg, Germany.
Gerlach
Manfred
M
Riederer
Peter
P
Baumeister
Ralf
R
Hoener
Marius C
MC
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000502:physiology*; D015259:Dopamine Agents / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D010641:Phenotype; D012402:Rotenone / Q000633:toxicity; D014475:Uncoupling Agents / Q000633:toxicity
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D014475:Uncoupling Agents; D012402:Rotenone; D049452:Green Fluorescent Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine