Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system

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Bibtex

@article{d56fb2867c1a4cc4a92d60ae2b2775bf,
title = "Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system",
abstract = "Genetic studies have implicated the neuronal ubiquitin C-terminal hydrolase (UCH) protein UCH-L1 in Parkinson's disease (PD) pathogenesis. Moreover, the function of UCH-L1 may be lost in the brains of PD and Alzheimer's disease patients. We have previously reported that the UCH-L1 polymorphic variant S18Y, potentially protective against PD in population studies, demonstrates specific antioxidant functions in cell culture. Albeit genetic, biochemical and neuropathological data support an association between UCH-L1, PD, synaptic degeneration and oxidative stress, the relationship between the dopaminergic system and UCH-L1 status remains obscure. In the current study, we have examined the dopaminergic system of mice lacking endogenous UCH-L1 protein (gracile axonal dystrophy mice). Our findings show that the lack of wild-type (WT) UCH-L1 does not influence to any significant degree the dopaminergic system at baseline or following injections of the neurotoxin methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, using a novel intrastriatal adenoviral injection protocol, we have found that mouse nigral neurons retrogradely transduced with S18Y UCH-L1, but not the WT protein, are significantly protected against MPTP toxicity. Overall, these data provide evidence for an antioxidant and neuroprotective effect of the S18Y variant of UCH-L1, but not of the WT protein, in the dopaminergic system, and may have implications for the pathogenesis of PD or related neurodegenerative conditions, in which oxidative stress might play a role.",
author = "Maria Xilouri and Elli Kyratzi and Pitychoutis, {Pothitos M.} and Zoi Papadopoulou-Daifoti and Celine Perier and Miquel Vila and Matina Maniati and Ayse Ulusoy and Deniz Kirik and Park, {David S.} and Keiji Wada and Leonidas Stefanis",
year = "2012",
doi = "10.1093/hmg/ddr521",
language = "English",
volume = "21",
pages = "874--889",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "4",

}