ParkinsonCanadaV1, PascalFrancis, Corpus, bibRecord, 000219

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

Identifieur interne : 000219 ( PascalFrancis/Corpus ); précédent : 000218; suivant : 000220

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

Auteurs : Maria Xilouri ; Elli Kyratzi ; Pothitos M. Pitychoutis ; Zoi Papadopoulou-Daifoti ; Celine Perier ; Miquel Vila ; Matina Maniati ; Ayse Ulusoy ; Deniz Kirik ; David S. Park ; Keiji Wada ; Leonidas Stefanis

Source :

Human molecular genetics : (Print) [ 0964-6906 ] ; 2012.

RBID : Pascal:12-0122767

Descripteurs français

Pascal (Inist)
- Neuroprotection, Polymorphisme, Variant, Variabilité génétique, Génotype, Génétique, Ubiquitin carboxy-terminal hydrolase L1.

English descriptors

KwdEn :
- Genetic variability, Genetics, Genotype, Neuroprotection, Polymorphism, Variant.

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.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

A01	`01`	`1`		`@0 0964-6906`
A03		`1`		`@0 Hum. mol. genet. : (Print)`
A05				`@2 21`
A06				`@2 4`
A08	`01`	`1`	`ENG`	`@1 Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system`
A11	`01`	`1`		`@1 XILOURI (Maria)`
A11	`02`	`1`		`@1 KYRATZI (Elli)`
A11	`03`	`1`		`@1 PITYCHOUTIS (Pothitos M.)`
A11	`04`	`1`		`@1 PAPADOPOULOU-DAIFOTI (Zoi)`
A11	`05`	`1`		`@1 PERIER (Celine)`
A11	`06`	`1`		`@1 VILA (Miquel)`
A11	`07`	`1`		`@1 MANIATI (Matina)`
A11	`08`	`1`		`@1 ULUSOY (Ayse)`
A11	`09`	`1`		`@1 KIRIK (Deniz)`
A11	`10`	`1`		`@1 PARK (David S.)`
A11	`11`	`1`		`@1 WADA (Keiji)`
A11	`12`	`1`		`@1 STEFANIS (Leonidas)`
A14	`01`			`@1 Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens @2 Athens @3 GRC @Z 1 aut. @Z 2 aut. @Z 7 aut. @Z 12 aut.`
A14	`02`			`@1 Department of Pharmacology, Medical School, University of Athens @2 Athens @3 GRC @Z 3 aut. @Z 4 aut.`
A14	`03`			`@1 Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) @2 Barcelona 08035 @3 ESP @Z 5 aut. @Z 6 aut.`
A14	`04`			`@1 Catalan Institution for Research and Advanced Studies (ICREA) @2 08010 Barcelona @3 ESP @Z 6 aut.`
A14	`05`			`@1 Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona @2 08193 Bellaterra, Barcelona @3 ESP @Z 6 aut.`
A14	`06`			`@1 Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University @2 Lund @3 SWE @Z 8 aut. @Z 9 aut.`
A14	`07`			`@1 Neuroscience Lab, University of Ottawa @2 Ottawa, ON @3 CAN @Z 10 aut.`
A14	`08`			`@1 Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry @2 Tokyo 187-8502 @3 JPN @Z 11 aut.`
A14	`09`			`@1 Second Department of Neurology, University of Athens Medical School @2 Athens @3 GRC @Z 12 aut.`
A20				`@1 874-889`
A21				`@1 2012`
A23	`01`			`@0 ENG`
A43	`01`			`@1 INIST @2 22540 @5 354000508403300130`
A44				`@0 0000 @1 © 2012 INIST-CNRS. All rights reserved.`
A45				`@0 66 ref.`
A47	`01`	`1`		`@0 12-0122767`
A60				`@1 P`
A61				`@0 A`
A64	`01`	`1`		`@0 Human molecular genetics : (Print)`
A66	`01`			`@0 GBR`
C01	`01`		`ENG`	@0 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.
C02	`01`	`X`		`@0 002A04`
C02	`02`	`X`		`@0 002A07`
C03	`01`	`X`	`FRE`	`@0 Neuroprotection @5 01`
C03	`01`	`X`	`ENG`	`@0 Neuroprotection @5 01`
C03	`01`	`X`	`SPA`	`@0 Neuroprotección @5 01`
C03	`02`	`X`	`FRE`	`@0 Polymorphisme @5 02`
C03	`02`	`X`	`ENG`	`@0 Polymorphism @5 02`
C03	`02`	`X`	`SPA`	`@0 Polimorfismo @5 02`
C03	`03`	`X`	`FRE`	`@0 Variant @5 03`
C03	`03`	`X`	`ENG`	`@0 Variant @5 03`
C03	`03`	`X`	`SPA`	`@0 Variante @5 03`
C03	`04`	`X`	`FRE`	`@0 Variabilité génétique @5 04`
C03	`04`	`X`	`ENG`	`@0 Genetic variability @5 04`
C03	`04`	`X`	`SPA`	`@0 Variabilidad genética @5 04`
C03	`05`	`X`	`FRE`	`@0 Génotype @5 05`
C03	`05`	`X`	`ENG`	`@0 Genotype @5 05`
C03	`05`	`X`	`SPA`	`@0 Genotipo @5 05`
C03	`06`	`X`	`FRE`	`@0 Génétique @5 06`
C03	`06`	`X`	`ENG`	`@0 Genetics @5 06`
C03	`06`	`X`	`SPA`	`@0 Genética @5 06`
C03	`07`	`X`	`FRE`	`@0 Ubiquitin carboxy-terminal hydrolase L1 @4 INC @5 88`
N21				`@1 093`
N44	`01`			`@1 OTO`
N82				`@1 OTO`

Format Inist (serveur)

NO :	PASCAL 12-0122767 INIST
ET :	Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system
AU :	XILOURI (Maria); KYRATZI (Elli); PITYCHOUTIS (Pothitos M.); PAPADOPOULOU-DAIFOTI (Zoi); PERIER (Celine); VILA (Miquel); MANIATI (Matina); ULUSOY (Ayse); KIRIK (Deniz); PARK (David S.); WADA (Keiji); STEFANIS (Leonidas)
AF :	Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens/Athens/Grèce (1 aut., 2 aut., 7 aut., 12 aut.); Department of Pharmacology, Medical School, University of Athens/Athens/Grèce (3 aut., 4 aut.); Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)/Barcelona 08035/Espagne (5 aut., 6 aut.); Catalan Institution for Research and Advanced Studies (ICREA)/08010 Barcelona/Espagne (6 aut.); Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona/08193 Bellaterra, Barcelona/Espagne (6 aut.); Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University/Lund/Suède (8 aut., 9 aut.); Neuroscience Lab, University of Ottawa/Ottawa, ON/Canada (10 aut.); Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry/Tokyo 187-8502/Japon (11 aut.); Second Department of Neurology, University of Athens Medical School/Athens/Grèce (12 aut.)
DT :	Publication en série; Niveau analytique
SO :	Human molecular genetics : (Print); ISSN 0964-6906; Royaume-Uni; Da. 2012; Vol. 21; No. 4; Pp. 874-889; Bibl. 66 ref.
LA :	Anglais
EA :	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.
CC :	002A04; 002A07
FD :	Neuroprotection; Polymorphisme; Variant; Variabilité génétique; Génotype; Génétique; Ubiquitin carboxy-terminal hydrolase L1
ED :	Neuroprotection; Polymorphism; Variant; Genetic variability; Genotype; Genetics
SD :	Neuroprotección; Polimorfismo; Variante; Variabilidad genética; Genotipo; Genética
LO :	INIST-22540.354000508403300130
ID :	12-0122767

Links to Exploration step

Pascal:12-0122767

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system</title>
<author><name sortKey="Xilouri, Maria" sort="Xilouri, Maria" uniqKey="Xilouri M" first="Maria" last="Xilouri">Maria Xilouri</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Kyratzi, Elli" sort="Kyratzi, Elli" uniqKey="Kyratzi E" first="Elli" last="Kyratzi">Elli Kyratzi</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Pitychoutis, Pothitos M" sort="Pitychoutis, Pothitos M" uniqKey="Pitychoutis P" first="Pothitos M." last="Pitychoutis">Pothitos M. Pitychoutis</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Pharmacology, Medical School, University of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Papadopoulou Daifoti, Zoi" sort="Papadopoulou Daifoti, Zoi" uniqKey="Papadopoulou Daifoti Z" first="Zoi" last="Papadopoulou-Daifoti">Zoi Papadopoulou-Daifoti</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Pharmacology, Medical School, University of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Perier, Celine" sort="Perier, Celine" uniqKey="Perier C" first="Celine" last="Perier">Celine Perier</name>
<affiliation><inist:fA14 i1="03"><s1>Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)</s1>
<s2>Barcelona 08035</s2>
<s3>ESP</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Vila, Miquel" sort="Vila, Miquel" uniqKey="Vila M" first="Miquel" last="Vila">Miquel Vila</name>
<affiliation><inist:fA14 i1="03"><s1>Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)</s1>
<s2>Barcelona 08035</s2>
<s3>ESP</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
<affiliation><inist:fA14 i1="04"><s1>Catalan Institution for Research and Advanced Studies (ICREA)</s1>
<s2>08010 Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
<affiliation><inist:fA14 i1="05"><s1>Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona</s1>
<s2>08193 Bellaterra, Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Maniati, Matina" sort="Maniati, Matina" uniqKey="Maniati M" first="Matina" last="Maniati">Matina Maniati</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Ulusoy, Ayse" sort="Ulusoy, Ayse" uniqKey="Ulusoy A" first="Ayse" last="Ulusoy">Ayse Ulusoy</name>
<affiliation><inist:fA14 i1="06"><s1>Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University</s1>
<s2>Lund</s2>
<s3>SWE</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Kirik, Deniz" sort="Kirik, Deniz" uniqKey="Kirik D" first="Deniz" last="Kirik">Deniz Kirik</name>
<affiliation><inist:fA14 i1="06"><s1>Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University</s1>
<s2>Lund</s2>
<s3>SWE</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<affiliation><inist:fA14 i1="07"><s1>Neuroscience Lab, University of Ottawa</s1>
<s2>Ottawa, ON</s2>
<s3>CAN</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Wada, Keiji" sort="Wada, Keiji" uniqKey="Wada K" first="Keiji" last="Wada">Keiji Wada</name>
<affiliation><inist:fA14 i1="08"><s1>Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry</s1>
<s2>Tokyo 187-8502</s2>
<s3>JPN</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
<affiliation><inist:fA14 i1="09"><s1>Second Department of Neurology, University of Athens Medical School</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">12-0122767</idno>
<date when="2012">2012</date>
<idno type="stanalyst">PASCAL 12-0122767 INIST</idno>
<idno type="RBID">Pascal:12-0122767</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000219</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system</title>
<author><name sortKey="Xilouri, Maria" sort="Xilouri, Maria" uniqKey="Xilouri M" first="Maria" last="Xilouri">Maria Xilouri</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Kyratzi, Elli" sort="Kyratzi, Elli" uniqKey="Kyratzi E" first="Elli" last="Kyratzi">Elli Kyratzi</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Pitychoutis, Pothitos M" sort="Pitychoutis, Pothitos M" uniqKey="Pitychoutis P" first="Pothitos M." last="Pitychoutis">Pothitos M. Pitychoutis</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Pharmacology, Medical School, University of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Papadopoulou Daifoti, Zoi" sort="Papadopoulou Daifoti, Zoi" uniqKey="Papadopoulou Daifoti Z" first="Zoi" last="Papadopoulou-Daifoti">Zoi Papadopoulou-Daifoti</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Pharmacology, Medical School, University of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Perier, Celine" sort="Perier, Celine" uniqKey="Perier C" first="Celine" last="Perier">Celine Perier</name>
<affiliation><inist:fA14 i1="03"><s1>Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)</s1>
<s2>Barcelona 08035</s2>
<s3>ESP</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Vila, Miquel" sort="Vila, Miquel" uniqKey="Vila M" first="Miquel" last="Vila">Miquel Vila</name>
<affiliation><inist:fA14 i1="03"><s1>Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)</s1>
<s2>Barcelona 08035</s2>
<s3>ESP</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
<affiliation><inist:fA14 i1="04"><s1>Catalan Institution for Research and Advanced Studies (ICREA)</s1>
<s2>08010 Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
<affiliation><inist:fA14 i1="05"><s1>Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona</s1>
<s2>08193 Bellaterra, Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Maniati, Matina" sort="Maniati, Matina" uniqKey="Maniati M" first="Matina" last="Maniati">Matina Maniati</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Ulusoy, Ayse" sort="Ulusoy, Ayse" uniqKey="Ulusoy A" first="Ayse" last="Ulusoy">Ayse Ulusoy</name>
<affiliation><inist:fA14 i1="06"><s1>Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University</s1>
<s2>Lund</s2>
<s3>SWE</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Kirik, Deniz" sort="Kirik, Deniz" uniqKey="Kirik D" first="Deniz" last="Kirik">Deniz Kirik</name>
<affiliation><inist:fA14 i1="06"><s1>Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University</s1>
<s2>Lund</s2>
<s3>SWE</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name>
<affiliation><inist:fA14 i1="07"><s1>Neuroscience Lab, University of Ottawa</s1>
<s2>Ottawa, ON</s2>
<s3>CAN</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Wada, Keiji" sort="Wada, Keiji" uniqKey="Wada K" first="Keiji" last="Wada">Keiji Wada</name>
<affiliation><inist:fA14 i1="08"><s1>Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry</s1>
<s2>Tokyo 187-8502</s2>
<s3>JPN</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name>
<affiliation><inist:fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
<affiliation><inist:fA14 i1="09"><s1>Second Department of Neurology, University of Athens Medical School</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
<idno type="ISSN">0964-6906</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
<idno type="ISSN">0964-6906</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Genetic variability</term>
<term>Genetics</term>
<term>Genotype</term>
<term>Neuroprotection</term>
<term>Polymorphism</term>
<term>Variant</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Neuroprotection</term>
<term>Polymorphisme</term>
<term>Variant</term>
<term>Variabilité génétique</term>
<term>Génotype</term>
<term>Génétique</term>
<term>Ubiquitin carboxy-terminal hydrolase L1</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0964-6906</s0>
</fA01>
<fA03 i2="1"><s0>Hum. mol. genet. : (Print)</s0>
</fA03>
<fA05><s2>21</s2>
</fA05>
<fA06><s2>4</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>XILOURI (Maria)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>KYRATZI (Elli)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>PITYCHOUTIS (Pothitos M.)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>PAPADOPOULOU-DAIFOTI (Zoi)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>PERIER (Celine)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>VILA (Miquel)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>MANIATI (Matina)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>ULUSOY (Ayse)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>KIRIK (Deniz)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>PARK (David S.)</s1>
</fA11>
<fA11 i1="11" i2="1"><s1>WADA (Keiji)</s1>
</fA11>
<fA11 i1="12" i2="1"><s1>STEFANIS (Leonidas)</s1>
</fA11>
<fA14 i1="01"><s1>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>12 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Department of Pharmacology, Medical School, University of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)</s1>
<s2>Barcelona 08035</s2>
<s3>ESP</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Catalan Institution for Research and Advanced Studies (ICREA)</s1>
<s2>08010 Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="05"><s1>Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona</s1>
<s2>08193 Bellaterra, Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="06"><s1>Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University</s1>
<s2>Lund</s2>
<s3>SWE</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="07"><s1>Neuroscience Lab, University of Ottawa</s1>
<s2>Ottawa, ON</s2>
<s3>CAN</s3>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="08"><s1>Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry</s1>
<s2>Tokyo 187-8502</s2>
<s3>JPN</s3>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="09"><s1>Second Department of Neurology, University of Athens Medical School</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>12 aut.</sZ>
</fA14>
<fA20><s1>874-889</s1>
</fA20>
<fA21><s1>2012</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>22540</s2>
<s5>354000508403300130</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2012 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>66 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>12-0122767</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Human molecular genetics : (Print)</s0>
</fA64>
<fA66 i1="01"><s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002A04</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002A07</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Neuroprotection</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Neuroprotection</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Neuroprotección</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Polymorphisme</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Polymorphism</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Polimorfismo</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Variant</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Variant</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Variante</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Variabilité génétique</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Genetic variability</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Variabilidad genética</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Génotype</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Genotype</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Genotipo</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Génétique</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Genetics</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Genética</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Ubiquitin carboxy-terminal hydrolase L1</s0>
<s4>INC</s4>
<s5>88</s5>
</fC03>
<fN21><s1>093</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
<server><NO>PASCAL 12-0122767 INIST</NO>
<ET>Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system</ET>
<AU>XILOURI (Maria); KYRATZI (Elli); PITYCHOUTIS (Pothitos M.); PAPADOPOULOU-DAIFOTI (Zoi); PERIER (Celine); VILA (Miquel); MANIATI (Matina); ULUSOY (Ayse); KIRIK (Deniz); PARK (David S.); WADA (Keiji); STEFANIS (Leonidas)</AU>
<AF>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens/Athens/Grèce (1 aut., 2 aut., 7 aut., 12 aut.); Department of Pharmacology, Medical School, University of Athens/Athens/Grèce (3 aut., 4 aut.); Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)/Barcelona 08035/Espagne (5 aut., 6 aut.); Catalan Institution for Research and Advanced Studies (ICREA)/08010 Barcelona/Espagne (6 aut.); Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona/08193 Bellaterra, Barcelona/Espagne (6 aut.); Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University/Lund/Suède (8 aut., 9 aut.); Neuroscience Lab, University of Ottawa/Ottawa, ON/Canada (10 aut.); Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry/Tokyo 187-8502/Japon (11 aut.); Second Department of Neurology, University of Athens Medical School/Athens/Grèce (12 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Human molecular genetics : (Print); ISSN 0964-6906; Royaume-Uni; Da. 2012; Vol. 21; No. 4; Pp. 874-889; Bibl. 66 ref.</SO>
<LA>Anglais</LA>
<EA>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.</EA>
<CC>002A04; 002A07</CC>
<FD>Neuroprotection; Polymorphisme; Variant; Variabilité génétique; Génotype; Génétique; Ubiquitin carboxy-terminal hydrolase L1</FD>
<ED>Neuroprotection; Polymorphism; Variant; Genetic variability; Genotype; Genetics</ED>
<SD>Neuroprotección; Polimorfismo; Variante; Variabilidad genética; Genotipo; Genética</SD>
<LO>INIST-22540.354000508403300130</LO>
<ID>12-0122767</ID>
</server>
</inist>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/PascalFrancis/Corpus

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000219 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Corpus/biblio.hfd -nk 000219 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Canada
   |area=    ParkinsonCanadaV1
   |flux=    PascalFrancis
   |étape=   Corpus
   |type=    RBID
   |clé=     Pascal:12-0122767
   |texte=   Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system
}}

This area was generated with Dilib version V0.6.29.
Data generation: Thu May 4 22:20:19 2017. Site generation: Fri Dec 23 23:17:26 2022

	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

La maladie de Parkinson au Canada (serveur d'exploration)

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

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

Source :

Descripteurs français

English descriptors

Abstract

Notice en format standard (ISO 2709)

Format Inist (serveur)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri