Parkinsonism-inducing neurotoxin MPP+: uptake and toxicity in nonneuronal COS cells expressing dopamine transporter

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S Kitayama1, S Shimada, G R Uhl

  • 1Laboratory of Molecular Neurobiology, Addiction Research Center/National Institute on Drug Abuse, Johns Hopkins University School of Medicine, Baltimore, MD. 21224.

Annals of Neurology
|July 1, 1992
PubMed

Insights

The dopamine transporter enables non-nerve cells to absorb the neurotoxin MPP+, which causes Parkinsonism. This finding suggests the dopamine transporter plays a crucial role in Parkinson's disease mechanisms.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Toxicology

Background:

  • Parkinsonism is a neurodegenerative disorder associated with dopamine neuron loss.
  • The neurotoxin MPP+ (1-methyl-4-phenylpyridinium) is implicated in Parkinsonism.
  • The dopamine transporter (DAT) is crucial for dopamine homeostasis.

Purpose of the Study:

  • To investigate the role of the dopamine transporter in MPP+ uptake and toxicity.
  • To determine if DAT can confer MPP+ sensitivity to non-neuronal cells.

Main Methods:

  • Cloned dopamine transporter complementary DNA was expressed in COS cells (primate kidney cells).
  • MPP+ accumulation and toxicity were measured in COS cells expressing DAT.

Main Results:

  • COS cells expressing DAT avidly accumulated MPP+.
  • MPP+ exposure resulted in toxicity in DAT-expressing COS cells.
  • Non-neuronal cells expressing DAT became sensitive to MPP+.

Conclusions:

  • The dopamine transporter can confer MPP+ sensitivity to non-neuronal cells.
  • DAT plays a significant role in the mechanisms underlying Parkinsonism.
  • Targeting DAT may offer therapeutic strategies for Parkinson's disease.

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