WldS mice are protected against the Parkinsonian mimetic MPTP

Daphne M. Hasbani, Karen L. O'Malley

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

The progressive loss of the nigrostriatal pathway is a distinguishing feature of Parkinson's disease. Because terminal field loss appears to precede cell body loss, we tested whether the mouse mutant WldS, which delays axonal degeneration in a variety of disorders, would ameliorate nigrostriatal degeneration following treatment with the Parkinsonian mimetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The present findings show that the WldS gene product enhances survival, prevents nigrostriatal axon degeneration, and attenuates neurotransmitter loss but does not rescue cell bodies. As MPTP is thought to impair mitochondrial energy production, these data suggest that disease pathology due to metabolic dysfunction could be improved by the WldS gene product. These results suggest new therapeutic avenues for Parkinson's disease.

Original languageEnglish
Pages (from-to)93-99
Number of pages7
JournalExperimental Neurology
Volume202
Issue number1
DOIs
StatePublished - Nov 2006

Keywords

  • MPTP
  • Neurodegeneration
  • Parkinson's disease
  • Wallerian degeneration

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