Lysosomal dysfunction in Parkinson disease
Identifieur interne : 000448 ( Hal/Checkpoint ); précédent : 000447; suivant : 000449Lysosomal dysfunction in Parkinson disease
Auteurs : Benjamin Dehay [France] ; Marta Martinez-Vicente [Espagne] ; Alfredo Ramirez [Allemagne] ; Celine Perier [Espagne] ; Christine Klein [Allemagne] ; Miquel Vila [Espagne] ; Erwan Bezard [France]Source :
- Autophagy [ 1554-8627 ] ; 2012-09.
Abstract
Mutations in ATP13A2 (PARK9) cause an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia called Kufor-Rakeb Syndrome (KRS). The ATP13A2 gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2) whose physiological function in mammalian cells, and hence its potential role in Parkinson disease (PD), remains elusive. In this context, we have recently shown that KRS-linked mutations in ATP13A2 leads to several lysosomal alterations in ATP13A2 KRS patient-derived fibroblasts, including impaired lysosomal acidification, decreased proteolytic processing of lysosomal enzymes, reduced degradation of lysosomal substrates and diminished lysosomal-mediated clearance of autophagosomes (AP). Similar alterations are observed in stable ATP13A2-knockdown dopaminergic cell lines, which are associated with cell death. Restoration of ATP13A2 levels in ATP13A2-mutant/depleted cells is able to restore lysosomal function and attenuate cell death. Relevant to PD, we have determined that ATP13A2 levels are decreased in dopaminergic nigral neurons from sporadic PD patients. Interestingly in these patients, the main signal of ATP13A2 is detected in the Lewy bodies. Our results unravel an instrumental role of ATP13A2 in lysosomal function and in cell viability. Altogether, our results validate ATP13A2 as a likely therapeutic target against PD degeneration.
Url:
DOI: 10.4161/auto.21011
Links toward previous steps (curation, corpus...)
Links to Exploration step
Hal:hal-01290069Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lysosomal dysfunction in Parkinson disease</title><author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName> <orgName type="acronym">IMN</orgName> <desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine> <country key="FR"></country> </address> <ref type="url">http://imn-bordeaux.org/</ref> </desc> <listRelation> <relation active="#struct-259761" type="direct"></relation> <relation name="UMR5293" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName> <orgName type="acronym">UB</orgName> <desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-bordeaux.fr/</ref> </desc></org></tutelle><tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Bordeaux</settlement><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Martinez Vicente, Marta" sort="Martinez Vicente, Marta" uniqKey="Martinez Vicente M" first="Marta" last="Martinez-Vicente">Marta Martinez-Vicente</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-260890" status="INCOMING"> <orgName>Neurodegenerative Diseases Research Group</orgName> <desc> <address> <addrLine>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases, Barcelona, Spain</addrLine> <country key="ES"></country> </address> </desc> <listRelation> <relation active="#struct-361966" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-361966" type="direct"><org type="institution" xml:id="struct-361966" status="INCOMING"> <orgName>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Espagne</country></affiliation></author><author><name sortKey="Ramirez, Alfredo" sort="Ramirez, Alfredo" uniqKey="Ramirez A" first="Alfredo" last="Ramirez">Alfredo Ramirez</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-262679" status="INCOMING"> <orgName>Section of Clinical and Molecular Neurogenetics</orgName> <desc> <address> <addrLine>Department of Neurology; University of Lübeck; Lübeck</addrLine> <country key="DE"></country> </address> </desc> <listRelation> <relation active="#struct-166039" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-166039" type="direct"><org type="institution" xml:id="struct-166039" status="VALID"> <orgName>Universität zu Lübeck [Lübeck]</orgName> <desc> <address> <addrLine>Ratzeburger Allee 16023562 Lübeck</addrLine> <country key="DE"></country> </address> <ref type="url">https://www.uni-luebeck.de/en/university/university.html</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>Allemagne</country></affiliation></author><author><name sortKey="Perier, Celine" sort="Perier, Celine" uniqKey="Perier C" first="Celine" last="Perier">Celine Perier</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-260891" status="INCOMING"> <orgName>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases</orgName> <orgName type="acronym">CIBERNED</orgName> <desc> <address> <addrLine>Barcelona Spain</addrLine> <country key="ES"></country> </address> </desc> <listRelation> <relation active="#struct-361966" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-361966" type="direct"><org type="institution" xml:id="struct-361966" status="INCOMING"> <orgName>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Espagne</country></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-101434" status="VALID"> <orgName>Software and System Architectures</orgName> <orgName type="acronym">Siemens AG Corporate Technology</orgName> <desc> <address> <addrLine>Günter-Scharowsky-Str. 1 91050 Erlangen Germany</addrLine> <country key="DE"></country> </address> </desc> <listRelation> <relation active="#struct-300755" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-300755" type="direct"><org type="institution" xml:id="struct-300755" status="VALID"> <orgName>Siemens AG [Munich]</orgName> <date type="start">2016-11-02</date> <desc> <address> <addrLine>Siemens AG (Headquarters)Wittelsbacherplatz 280333 MunichGermany</addrLine> <country key="DE"></country> </address> <ref type="url">https://www.siemens.com/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>Allemagne</country></affiliation></author><author><name sortKey="Vila, Miquel" sort="Vila, Miquel" uniqKey="Vila M" first="Miquel" last="Vila">Miquel Vila</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-203500" status="VALID"> <orgName>Department of Computer Science and Artificial Intelligence</orgName> <orgName type="acronym">DECSAI</orgName> <desc> <address> <addrLine>Hight Technical School of Computer Sencie and Telecommunications Calle del Periodista Daniel Saucedo Aranda 18014 Granada</addrLine> <country key="ES"></country> </address> <ref type="url">http://decsai.ugr.es/index.php</ref> </desc> <listRelation> <relation active="#struct-315919" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-315919" type="direct"><org type="institution" xml:id="struct-315919" status="INCOMING"> <orgName>University of Granada</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Espagne</country><placeName><settlement type="city">Grenade (Espagne)</settlement><region nuts="2" type="region">Andalousie</region></placeName><orgName type="university">Université de Grenade</orgName></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName> <orgName type="acronym">IMN</orgName> <desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine> <country key="FR"></country> </address> <ref type="url">http://imn-bordeaux.org/</ref> </desc> <listRelation> <relation active="#struct-259761" type="direct"></relation> <relation name="UMR5293" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName> <orgName type="acronym">UB</orgName> <desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-bordeaux.fr/</ref> </desc></org></tutelle><tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Bordeaux</settlement><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:hal-01290069</idno><idno type="halId">hal-01290069</idno><idno type="halUri">https://hal.archives-ouvertes.fr/hal-01290069</idno><idno type="url">https://hal.archives-ouvertes.fr/hal-01290069</idno><idno type="doi">10.4161/auto.21011</idno><date when="2012-09">2012-09</date><idno type="wicri:Area/Hal/Corpus">000646</idno><idno type="wicri:Area/Hal/Curation">000646</idno><idno type="wicri:Area/Hal/Checkpoint">000448</idno><idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000448</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Lysosomal dysfunction in Parkinson disease</title><author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName> <orgName type="acronym">IMN</orgName> <desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine> <country key="FR"></country> </address> <ref type="url">http://imn-bordeaux.org/</ref> </desc> <listRelation> <relation active="#struct-259761" type="direct"></relation> <relation name="UMR5293" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName> <orgName type="acronym">UB</orgName> <desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-bordeaux.fr/</ref> </desc></org></tutelle><tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Bordeaux</settlement><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author><author><name sortKey="Martinez Vicente, Marta" sort="Martinez Vicente, Marta" uniqKey="Martinez Vicente M" first="Marta" last="Martinez-Vicente">Marta Martinez-Vicente</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-260890" status="INCOMING"> <orgName>Neurodegenerative Diseases Research Group</orgName> <desc> <address> <addrLine>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases, Barcelona, Spain</addrLine> <country key="ES"></country> </address> </desc> <listRelation> <relation active="#struct-361966" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-361966" type="direct"><org type="institution" xml:id="struct-361966" status="INCOMING"> <orgName>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Espagne</country></affiliation></author><author><name sortKey="Ramirez, Alfredo" sort="Ramirez, Alfredo" uniqKey="Ramirez A" first="Alfredo" last="Ramirez">Alfredo Ramirez</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-262679" status="INCOMING"> <orgName>Section of Clinical and Molecular Neurogenetics</orgName> <desc> <address> <addrLine>Department of Neurology; University of Lübeck; Lübeck</addrLine> <country key="DE"></country> </address> </desc> <listRelation> <relation active="#struct-166039" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-166039" type="direct"><org type="institution" xml:id="struct-166039" status="VALID"> <orgName>Universität zu Lübeck [Lübeck]</orgName> <desc> <address> <addrLine>Ratzeburger Allee 16023562 Lübeck</addrLine> <country key="DE"></country> </address> <ref type="url">https://www.uni-luebeck.de/en/university/university.html</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>Allemagne</country></affiliation></author><author><name sortKey="Perier, Celine" sort="Perier, Celine" uniqKey="Perier C" first="Celine" last="Perier">Celine Perier</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-260891" status="INCOMING"> <orgName>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases</orgName> <orgName type="acronym">CIBERNED</orgName> <desc> <address> <addrLine>Barcelona Spain</addrLine> <country key="ES"></country> </address> </desc> <listRelation> <relation active="#struct-361966" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-361966" type="direct"><org type="institution" xml:id="struct-361966" status="INCOMING"> <orgName>Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Espagne</country></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-101434" status="VALID"> <orgName>Software and System Architectures</orgName> <orgName type="acronym">Siemens AG Corporate Technology</orgName> <desc> <address> <addrLine>Günter-Scharowsky-Str. 1 91050 Erlangen Germany</addrLine> <country key="DE"></country> </address> </desc> <listRelation> <relation active="#struct-300755" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-300755" type="direct"><org type="institution" xml:id="struct-300755" status="VALID"> <orgName>Siemens AG [Munich]</orgName> <date type="start">2016-11-02</date> <desc> <address> <addrLine>Siemens AG (Headquarters)Wittelsbacherplatz 280333 MunichGermany</addrLine> <country key="DE"></country> </address> <ref type="url">https://www.siemens.com/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>Allemagne</country></affiliation></author><author><name sortKey="Vila, Miquel" sort="Vila, Miquel" uniqKey="Vila M" first="Miquel" last="Vila">Miquel Vila</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-203500" status="VALID"> <orgName>Department of Computer Science and Artificial Intelligence</orgName> <orgName type="acronym">DECSAI</orgName> <desc> <address> <addrLine>Hight Technical School of Computer Sencie and Telecommunications Calle del Periodista Daniel Saucedo Aranda 18014 Granada</addrLine> <country key="ES"></country> </address> <ref type="url">http://decsai.ugr.es/index.php</ref> </desc> <listRelation> <relation active="#struct-315919" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-315919" type="direct"><org type="institution" xml:id="struct-315919" status="INCOMING"> <orgName>University of Granada</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Espagne</country><placeName><settlement type="city">Grenade (Espagne)</settlement><region nuts="2" type="region">Andalousie</region></placeName><orgName type="university">Université de Grenade</orgName></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName> <orgName type="acronym">IMN</orgName> <desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine> <country key="FR"></country> </address> <ref type="url">http://imn-bordeaux.org/</ref> </desc> <listRelation> <relation active="#struct-259761" type="direct"></relation> <relation name="UMR5293" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName> <orgName type="acronym">UB</orgName> <desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-bordeaux.fr/</ref> </desc></org></tutelle><tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Bordeaux</settlement><region type="region" nuts="2">Nouvelle-Aquitaine</region><region type="old region" nuts="2">Aquitaine</region></placeName><orgName type="university">Université de Bordeaux</orgName></affiliation></author></analytic><idno type="DOI">10.4161/auto.21011</idno><series><title level="j">Autophagy</title><idno type="ISSN">1554-8627</idno><imprint><date type="datePub">2012-09</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in ATP13A2 (PARK9) cause an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia called Kufor-Rakeb Syndrome (KRS). The ATP13A2 gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2) whose physiological function in mammalian cells, and hence its potential role in Parkinson disease (PD), remains elusive. In this context, we have recently shown that KRS-linked mutations in ATP13A2 leads to several lysosomal alterations in ATP13A2 KRS patient-derived fibroblasts, including impaired lysosomal acidification, decreased proteolytic processing of lysosomal enzymes, reduced degradation of lysosomal substrates and diminished lysosomal-mediated clearance of autophagosomes (AP). Similar alterations are observed in stable ATP13A2-knockdown dopaminergic cell lines, which are associated with cell death. Restoration of ATP13A2 levels in ATP13A2-mutant/depleted cells is able to restore lysosomal function and attenuate cell death. Relevant to PD, we have determined that ATP13A2 levels are decreased in dopaminergic nigral neurons from sporadic PD patients. Interestingly in these patients, the main signal of ATP13A2 is detected in the Lewy bodies. Our results unravel an instrumental role of ATP13A2 in lysosomal function and in cell viability. Altogether, our results validate ATP13A2 as a likely therapeutic target against PD degeneration.</div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">Lysosomal dysfunction in Parkinson disease</title> <author role="aut"> <persName> <forename type="first">Benjamin</forename> <surname>Dehay</surname> </persName> <idno type="halauthorid">159357</idno> <affiliation ref="#struct-244085"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marta</forename> <surname>Martinez-Vicente</surname> </persName> <idno type="halauthorid">765979</idno> <affiliation ref="#struct-260890"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alfredo</forename> <surname>Ramirez</surname> </persName> <idno type="halauthorid">1061243</idno> <affiliation ref="#struct-262679"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Celine</forename> <surname>Perier</surname> </persName> <idno type="halauthorid">1053468</idno> <affiliation ref="#struct-260891"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Christine</forename> <surname>Klein</surname> </persName> <idno type="halauthorid">410300</idno> <affiliation ref="#struct-101434"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Miquel</forename> <surname>Vila</surname> </persName> <idno type="halauthorid">766334</idno> <affiliation ref="#struct-203500"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Erwan</forename> <surname>Bezard</surname> </persName> <idno type="halauthorid">537314</idno> <affiliation ref="#struct-244085"></affiliation> </author> <editor role="depositor"> <persName> <forename>Chantal</forename> <surname>GUERIN</surname> </persName> <email type="md5">eb4bde61f74652335183b0bd05630b2c</email> <email type="domain">u-bordeaux.fr</email> </editor> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2016-03-17 15:25:19</date> <date type="whenModified">2016-03-18 01:00:30</date> <date type="whenReleased">2016-03-17 15:25:19</date> <date type="whenProduced">2012-09</date> </edition> <respStmt> <resp>contributor</resp> <name key="321070"> <persName> <forename>Chantal</forename> <surname>GUERIN</surname> </persName> <email type="md5">eb4bde61f74652335183b0bd05630b2c</email> <email type="domain">u-bordeaux.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">hal-01290069</idno> <idno type="halUri">https://hal.archives-ouvertes.fr/hal-01290069</idno> <idno type="halBibtex">dehay:hal-01290069</idno> <idno type="halRefHtml">Autophagy, Taylor & Francis, 2012, 8 (9), <10.4161/auto.21011></idno> <idno type="halRef">Autophagy, Taylor & Francis, 2012, 8 (9), <10.4161/auto.21011></idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno> </seriesStmt> <notesStmt> <note type="audience" n="2">International</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Lysosomal dysfunction in Parkinson disease</title> <author role="aut"> <persName> <forename type="first">Benjamin</forename> <surname>Dehay</surname> </persName> <idno type="halauthorid">159357</idno> <affiliation ref="#struct-244085"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marta</forename> <surname>Martinez-Vicente</surname> </persName> <idno type="halauthorid">765979</idno> <affiliation ref="#struct-260890"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alfredo</forename> <surname>Ramirez</surname> </persName> <idno type="halauthorid">1061243</idno> <affiliation ref="#struct-262679"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Celine</forename> <surname>Perier</surname> </persName> <idno type="halauthorid">1053468</idno> <affiliation ref="#struct-260891"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Christine</forename> <surname>Klein</surname> </persName> <idno type="halauthorid">410300</idno> <affiliation ref="#struct-101434"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Miquel</forename> <surname>Vila</surname> </persName> <idno type="halauthorid">766334</idno> <affiliation ref="#struct-203500"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Erwan</forename> <surname>Bezard</surname> </persName> <idno type="halauthorid">537314</idno> <affiliation ref="#struct-244085"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="VALID">28676</idno> <idno type="issn">1554-8627</idno> <idno type="eissn">1554-8635</idno> <title level="j">Autophagy</title> <imprint> <publisher>Taylor & Francis</publisher> <biblScope unit="volume">8</biblScope> <biblScope unit="issue">9</biblScope> <date type="datePub">2012-09</date> </imprint> </monogr> <idno type="doi">10.4161/auto.21011</idno> <idno type="pubmed">22885599</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <abstract xml:lang="en">Mutations in ATP13A2 (PARK9) cause an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia called Kufor-Rakeb Syndrome (KRS). The ATP13A2 gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2) whose physiological function in mammalian cells, and hence its potential role in Parkinson disease (PD), remains elusive. In this context, we have recently shown that KRS-linked mutations in ATP13A2 leads to several lysosomal alterations in ATP13A2 KRS patient-derived fibroblasts, including impaired lysosomal acidification, decreased proteolytic processing of lysosomal enzymes, reduced degradation of lysosomal substrates and diminished lysosomal-mediated clearance of autophagosomes (AP). Similar alterations are observed in stable ATP13A2-knockdown dopaminergic cell lines, which are associated with cell death. Restoration of ATP13A2 levels in ATP13A2-mutant/depleted cells is able to restore lysosomal function and attenuate cell death. Relevant to PD, we have determined that ATP13A2 levels are decreased in dopaminergic nigral neurons from sporadic PD patients. Interestingly in these patients, the main signal of ATP13A2 is detected in the Lewy bodies. Our results unravel an instrumental role of ATP13A2 in lysosomal function and in cell viability. Altogether, our results validate ATP13A2 as a likely therapeutic target against PD degeneration.</abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Hal/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000448 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Hal/Checkpoint/biblio.hfd -nk 000448 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= Hal
|étape= Checkpoint
|type= RBID
|clé= Hal:hal-01290069
|texte= Lysosomal dysfunction in Parkinson disease
}}
| This area was generated with Dilib version V0.6.29. |  |