Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl-phenyl-tetrahydropyridine toxicity

Bruno Conti, Shuei Sugama, Jacinta Lucero, Raphaelle Winsky-Sommerer, Sebastian A. Wirz, Pamela Maher, Zane Andrews, Alasdair M. Barr, Maria C. Morale, Covadonga Paneda, Janell Pemberton, Svetlana Gaidarova, M. Margarita Behrens, Flint Beal, Pietro Paolo Sanna, Tamas L. Horvath, Tamas Bartfai

Research output: Contribution to journalArticle

Abstract

Oxidative stress is implicated in the death of dopaminergic neurons in sporadic forms of Parkinson's disease. Because oxidative stress can be modulated endogenously by uncoupling proteins (UCPs), we hypothesized that specific neuronal expression of UCP2, one member of the UCP family that is rapidly induced in the CNS following insults, could confer neuroprotection in a mouse model of Parkinson's disease. We generated transgenic mice overexpressing UCP2 in catecholaminergic neurons under the control of the tyrosine hydroxylase promoter (TH-UCP2). In these mice, dopaminergic neurons of the substantia nigra showed a twofold elevation in UCP2 expression, elevated uncoupling of their mitochondria, and a marked reduction in indicators of oxidative stress, an effect also observed in the striatum. Upon acute exposure to 1,2,3,6-methyl-phenyl-tetrahydropyridine, TH-UCP2 mice showed neuroprotection and retention of locomotor functions. Our data suggest that UCP2 may represent a drug target for slowing the progression of Parkinson's disease.

Original languageEnglish
Pages (from-to)493-501
Number of pages9
JournalJournal of Neurochemistry
Volume93
Issue number2
DOIs
Publication statusPublished - Apr 2005

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Keywords

  • MPTP
  • Parkinson
  • Uncoupling protein 2

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Conti, B., Sugama, S., Lucero, J., Winsky-Sommerer, R., Wirz, S. A., Maher, P., Andrews, Z., Barr, A. M., Morale, M. C., Paneda, C., Pemberton, J., Gaidarova, S., Behrens, M. M., Beal, F., Sanna, P. P., Horvath, T. L., & Bartfai, T. (2005). Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl-phenyl-tetrahydropyridine toxicity. Journal of Neurochemistry, 93(2), 493-501. https://doi.org/10.1111/j.1471-4159.2005.03052.x