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Selective neuroprot...
Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system
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Xilouri, Maria (author)
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Kyratzi, Elli (author)
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Pitychoutis, Pothitos M. (author)
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Papadopoulou-Daifoti, Zoi (author)
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Perier, Celine (author)
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Vila, Miquel (author)
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Maniati, Matina (author)
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- Ulusoy, Ayse (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Kirik, Deniz (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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Park, David S. (author)
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Wada, Keiji (author)
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Stefanis, Leonidas (author)
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(creator_code:org_t)
- 2011-11-10
- 2012
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:4, s. 874-889
- Related links:
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http://dx.doi.org/10...
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https://academic.oup...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Xilouri, Maria
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Kyratzi, Elli
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Pitychoutis, Pot ...
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Papadopoulou-Dai ...
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Perier, Celine
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Vila, Miquel
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Maniati, Matina
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Ulusoy, Ayse
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Kirik, Deniz
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Park, David S.
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Wada, Keiji
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Stefanis, Leonid ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Human Molecular ...
- By the university
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Lund University