Premium
Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6‐methyl‐phenyl‐tetrahydropyridine toxicity
Author(s) -
Conti Bruno,
Sugama Shuei,
Lucero Jacinta,
WinskySommerer Raphaelle,
Wirz Sebastian A.,
Maher Pamela,
Andrews Zane,
Barr Alasdair M.,
Morale Maria C.,
Paneda Covadonga,
Pemberton Janell,
Gaidarova Svetlana,
Behrens M. Margarita,
Beal Flint,
Sanna Pietro Paolo,
Horvath Tamas,
Bartfai Tamas
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03052.x
Subject(s) - substantia nigra , dopaminergic , neuroprotection , oxidative stress , tyrosine hydroxylase , striatum , mptp , biology , parkinson's disease , endocrinology , dopamine , catecholaminergic , medicine , catecholaminergic cell groups , neurotoxicity , genetically modified mouse , neuroscience , transgene , toxicity , biochemistry , disease , gene
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.