1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase

J Neurosci Res. 2006 Feb 1;83(2):233-42. doi: 10.1002/jnr.20696.


Oxidative stress has been suggested to be an important mediator of dopaminergic cell death in Parkinson's disease (PD). We investigated the neuroprotective potential of Cu/Zn superoxide dismutase (SOD1) overexpression in the rat substantia nigra (SN) following adenovirus-mediated gene transfer. Human dopaminergic SK-N-SH cells were transduced with adenoviral vectors expressing either human SOD1 (Ad-SOD1) or beta-galactosidase (Ad-betagal) before exposure to 1 mM of the 1-methyl-4-phenylpyridinium ion (MPP+). A strong neuroprotective effect of SOD1 gene transfer was observed in the SK-N-SH cells exposed to MPP+ compared with controls. Adult rats were then given unilateral injections of either Ad-SOD1 or Ad-betagal into the striatum, and MPP+ was administered 8 days later at the same location. Strong transgene expression was detected in the SN dopaminergic neurons, a consequence of retrograde axonal transport of the adenoviral particles. The amphetamine-induced rotational behavior of the rats was markedly lower in Ad-SOD1-injected rats than in control animals. Also, behavioral recovery significantly correlated with the number of tyrosine hydrolase-expressing neurons in the SN of the treated rats. These results are consistent with oxidative stress contributing to the MPP+ -induced neurodegenerative process. They also indicate that SOD1 gene transfer into the nigrostriatal system may be a potential neuroprotective strategy for treating PD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Animals
  • Cell Count / methods
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors / physiology
  • Humans
  • Immunohistochemistry / methods
  • Motor Activity / physiology
  • Neuroblastoma
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / therapy*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Parkinson Disease / therapy
  • Rats
  • Rotarod Performance Test / methods
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase / therapeutic use*
  • Tetrazolium Salts
  • Thiazoles
  • Transgenes / physiology
  • Tyrosine 3-Monooxygenase / metabolism


  • Tetrazolium Salts
  • Thiazoles
  • Tyrosine 3-Monooxygenase
  • Superoxide Dismutase
  • thiazolyl blue
  • 1-Methyl-4-phenylpyridinium