Cellular Redox Systems Impact the Aggregation of Cu,Zn Superoxide Dismutase Linked to Familial Amyotrophic Lateral Sclerosis.
Identifieur interne : 000474 ( Main/Exploration ); précédent : 000473; suivant : 000475Cellular Redox Systems Impact the Aggregation of Cu,Zn Superoxide Dismutase Linked to Familial Amyotrophic Lateral Sclerosis.
Auteurs : Cristina Álvarez-Zaldiernas [Espagne] ; Jun Lu [République populaire de Chine] ; Yujuan Zheng [Suède] ; Hongqian Yang [Suède] ; Juan Blasi [Espagne] ; Carles Solsona [États-Unis] ; Arne Holmgren [Suède]Source :
- The Journal of biological chemistry [ 1083-351X ] ; 2016.
Descripteurs français
- KwdFr :
- Agrégation pathologique de protéines (enzymologie), Agrégation pathologique de protéines (génétique), Animaux (MeSH), Glutarédoxines (génétique), Glutarédoxines (métabolisme), Humains (MeSH), Lignée cellulaire tumorale (MeSH), Mutation faux-sens (MeSH), Oxydoréduction (MeSH), Pliage des protéines (MeSH), Rats (MeSH), Sclérose latérale amyotrophique (enzymologie), Sclérose latérale amyotrophique (génétique), Stress oxydatif (MeSH), Substitution d'acide aminé (MeSH), Superoxide dismutase-1 (génétique), Superoxide dismutase-1 (métabolisme), Thiorédoxines (génétique), Thiorédoxines (métabolisme).
- MESH :
- enzymologie : Agrégation pathologique de protéines, Sclérose latérale amyotrophique.
- génétique : Agrégation pathologique de protéines, Glutarédoxines, Sclérose latérale amyotrophique, Superoxide dismutase-1, Thiorédoxines.
- métabolisme : Glutarédoxines, Superoxide dismutase-1, Thiorédoxines.
- Animaux, Humains, Lignée cellulaire tumorale, Mutation faux-sens, Oxydoréduction, Pliage des protéines, Rats, Stress oxydatif, Substitution d'acide aminé.
English descriptors
- KwdEn :
- Amino Acid Substitution (MeSH), Amyotrophic Lateral Sclerosis (enzymology), Amyotrophic Lateral Sclerosis (genetics), Animals (MeSH), Cell Line, Tumor (MeSH), Glutaredoxins (genetics), Glutaredoxins (metabolism), Humans (MeSH), Mutation, Missense (MeSH), Oxidation-Reduction (MeSH), Oxidative Stress (MeSH), Protein Aggregation, Pathological (enzymology), Protein Aggregation, Pathological (genetics), Protein Folding (MeSH), Rats (MeSH), Superoxide Dismutase-1 (genetics), Superoxide Dismutase-1 (metabolism), Thioredoxins (genetics), Thioredoxins (metabolism).
- MESH :
- chemical , genetics : Glutaredoxins, Superoxide Dismutase-1, Thioredoxins.
- enzymology : Amyotrophic Lateral Sclerosis, Protein Aggregation, Pathological.
- genetics : Amyotrophic Lateral Sclerosis, Protein Aggregation, Pathological.
- chemical , metabolism : Glutaredoxins, Superoxide Dismutase-1, Thioredoxins.
- Amino Acid Substitution, Animals, Cell Line, Tumor, Humans, Mutation, Missense, Oxidation-Reduction, Oxidative Stress, Protein Folding, Rats.
Abstract
Protein misfolding is implicated in neurodegenerative diseases such as ALS, where mutations of superoxide dismutase 1 (SOD1) account for about 20% of the inherited mutations. Human SOD1 (hSOD1) contains four cysteines, including Cys(57) and Cys(146), which have been linked to protein stability and folding via forming a disulfide bond, and Cys(6) and Cys(111) as free thiols. But the roles of the cellular oxidation-reduction (redox) environment in SOD1 folding and aggregation are not well understood. Here we explore the effects of cellular redox systems on the aggregation of hSOD1 proteins. We found that the known hSOD1 mutations G93A and A4V increased the capability of the thioredoxin and glutaredoxin systems to reduce hSOD1 compared with wild-type hSOD1. Treatment with inhibitors of these redox systems resulted in an increase of hSOD1 aggregates in the cytoplasm of cells transfected with mutants but not in cells transfected with wild-type hSOD1 or those containing a secondary C111G mutation. This aggregation may be coupled to changes in the redox state of the G93A and A4V mutants upon mild oxidative stress. These results strongly suggest that the thioredoxin and glutaredoxin systems are the key regulators for hSOD1 aggregation and may play critical roles in the pathogenesis of ALS.
DOI: 10.1074/jbc.M115.708230
PubMed: 27261461
PubMed Central: PMC5016121
Affiliations:
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Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona, Spain solsona@ub.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. 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Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden, the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona</wicri:regionArea><placeName><region nuts="2" type="communauté">Catalogne</region></placeName></affiliation></author><author><name sortKey="Lu, Jun" sort="Lu, Jun" uniqKey="Lu J" first="Jun" last="Lu">Jun Lu</name><affiliation wicri:level="1"><nlm:affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden, junlu@swu.edu.cn.</nlm:affiliation><country wicri:rule="url">République populaire de Chine</country><wicri:regionArea>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden</wicri:regionArea><wicri:noRegion>Sweden</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Yujuan" sort="Zheng, Yujuan" uniqKey="Zheng Y" first="Yujuan" last="Zheng">Yujuan Zheng</name><affiliation wicri:level="3"><nlm:affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Yang, Hongqian" sort="Yang, Hongqian" uniqKey="Yang H" first="Hongqian" last="Yang">Hongqian Yang</name><affiliation wicri:level="3"><nlm:affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Blasi, Juan" sort="Blasi, Juan" uniqKey="Blasi J" first="Juan" last="Blasi">Juan Blasi</name><affiliation wicri:level="2"><nlm:affiliation>the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona</wicri:regionArea><placeName><region nuts="2" type="communauté">Catalogne</region></placeName></affiliation></author><author><name sortKey="Solsona, Carles" sort="Solsona, Carles" uniqKey="Solsona C" first="Carles" last="Solsona">Carles Solsona</name><affiliation wicri:level="1"><nlm:affiliation>the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona, Spain solsona@ub.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona</wicri:regionArea><wicri:noRegion>08908 Barcelona</wicri:noRegion></affiliation></author><author><name sortKey="Holmgren, Arne" sort="Holmgren, Arne" uniqKey="Holmgren A" first="Arne" last="Holmgren">Arne Holmgren</name><affiliation wicri:level="1"><nlm:affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden, arne.holmgren@ki.se.</nlm:affiliation><country wicri:rule="url">Suède</country><wicri:regionArea>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden</wicri:regionArea><wicri:noRegion>Sweden</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution (MeSH)</term><term>Amyotrophic Lateral Sclerosis (enzymology)</term><term>Amyotrophic Lateral Sclerosis (genetics)</term><term>Animals (MeSH)</term><term>Cell Line, Tumor (MeSH)</term><term>Glutaredoxins (genetics)</term><term>Glutaredoxins (metabolism)</term><term>Humans (MeSH)</term><term>Mutation, Missense (MeSH)</term><term>Oxidation-Reduction (MeSH)</term><term>Oxidative Stress (MeSH)</term><term>Protein Aggregation, Pathological (enzymology)</term><term>Protein Aggregation, Pathological (genetics)</term><term>Protein Folding (MeSH)</term><term>Rats (MeSH)</term><term>Superoxide Dismutase-1 (genetics)</term><term>Superoxide Dismutase-1 (metabolism)</term><term>Thioredoxins (genetics)</term><term>Thioredoxins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Agrégation pathologique de protéines (enzymologie)</term><term>Agrégation pathologique de protéines (génétique)</term><term>Animaux (MeSH)</term><term>Glutarédoxines (génétique)</term><term>Glutarédoxines (métabolisme)</term><term>Humains (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Mutation faux-sens (MeSH)</term><term>Oxydoréduction (MeSH)</term><term>Pliage des protéines (MeSH)</term><term>Rats (MeSH)</term><term>Sclérose latérale amyotrophique (enzymologie)</term><term>Sclérose latérale amyotrophique (génétique)</term><term>Stress oxydatif (MeSH)</term><term>Substitution d'acide aminé (MeSH)</term><term>Superoxide dismutase-1 (génétique)</term><term>Superoxide dismutase-1 (métabolisme)</term><term>Thiorédoxines (génétique)</term><term>Thiorédoxines (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glutaredoxins</term><term>Superoxide Dismutase-1</term><term>Thioredoxins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Agrégation pathologique de protéines</term><term>Sclérose latérale amyotrophique</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Amyotrophic Lateral Sclerosis</term><term>Protein Aggregation, Pathological</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Amyotrophic Lateral Sclerosis</term><term>Protein Aggregation, Pathological</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Agrégation pathologique de protéines</term><term>Glutarédoxines</term><term>Sclérose latérale amyotrophique</term><term>Superoxide dismutase-1</term><term>Thiorédoxines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glutaredoxins</term><term>Superoxide Dismutase-1</term><term>Thioredoxins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glutarédoxines</term><term>Superoxide dismutase-1</term><term>Thiorédoxines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Cell Line, Tumor</term><term>Humans</term><term>Mutation, Missense</term><term>Oxidation-Reduction</term><term>Oxidative Stress</term><term>Protein Folding</term><term>Rats</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mutation faux-sens</term><term>Oxydoréduction</term><term>Pliage des protéines</term><term>Rats</term><term>Stress oxydatif</term><term>Substitution d'acide aminé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Protein misfolding is implicated in neurodegenerative diseases such as ALS, where mutations of superoxide dismutase 1 (SOD1) account for about 20% of the inherited mutations. Human SOD1 (hSOD1) contains four cysteines, including Cys(57) and Cys(146), which have been linked to protein stability and folding via forming a disulfide bond, and Cys(6) and Cys(111) as free thiols. But the roles of the cellular oxidation-reduction (redox) environment in SOD1 folding and aggregation are not well understood. Here we explore the effects of cellular redox systems on the aggregation of hSOD1 proteins. We found that the known hSOD1 mutations G93A and A4V increased the capability of the thioredoxin and glutaredoxin systems to reduce hSOD1 compared with wild-type hSOD1. Treatment with inhibitors of these redox systems resulted in an increase of hSOD1 aggregates in the cytoplasm of cells transfected with mutants but not in cells transfected with wild-type hSOD1 or those containing a secondary C111G mutation. This aggregation may be coupled to changes in the redox state of the G93A and A4V mutants upon mild oxidative stress. These results strongly suggest that the thioredoxin and glutaredoxin systems are the key regulators for hSOD1 aggregation and may play critical roles in the pathogenesis of ALS.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27261461</PMID><DateCompleted><Year>2017</Year><Month>05</Month><Day>03</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1083-351X</ISSN><JournalIssue CitedMedium="Internet"><Volume>291</Volume><Issue>33</Issue><PubDate><Year>2016</Year><Month>08</Month><Day>12</Day></PubDate></JournalIssue><Title>The Journal of biological chemistry</Title><ISOAbbreviation>J Biol Chem</ISOAbbreviation></Journal><ArticleTitle>Cellular Redox Systems Impact the Aggregation of Cu,Zn Superoxide Dismutase Linked to Familial Amyotrophic Lateral Sclerosis.</ArticleTitle><Pagination><MedlinePgn>17197-208</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1074/jbc.M115.708230</ELocationID><Abstract><AbstractText>Protein misfolding is implicated in neurodegenerative diseases such as ALS, where mutations of superoxide dismutase 1 (SOD1) account for about 20% of the inherited mutations. Human SOD1 (hSOD1) contains four cysteines, including Cys(57) and Cys(146), which have been linked to protein stability and folding via forming a disulfide bond, and Cys(6) and Cys(111) as free thiols. But the roles of the cellular oxidation-reduction (redox) environment in SOD1 folding and aggregation are not well understood. Here we explore the effects of cellular redox systems on the aggregation of hSOD1 proteins. We found that the known hSOD1 mutations G93A and A4V increased the capability of the thioredoxin and glutaredoxin systems to reduce hSOD1 compared with wild-type hSOD1. Treatment with inhibitors of these redox systems resulted in an increase of hSOD1 aggregates in the cytoplasm of cells transfected with mutants but not in cells transfected with wild-type hSOD1 or those containing a secondary C111G mutation. This aggregation may be coupled to changes in the redox state of the G93A and A4V mutants upon mild oxidative stress. These results strongly suggest that the thioredoxin and glutaredoxin systems are the key regulators for hSOD1 aggregation and may play critical roles in the pathogenesis of ALS.</AbstractText><CopyrightInformation>© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Álvarez-Zaldiernas</LastName><ForeName>Cristina</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden, the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden, junlu@swu.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Yujuan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Hongqian</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blasi</LastName><ForeName>Juan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Solsona</LastName><ForeName>Carles</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>the Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Campus Bellvitge, University of Barcelona, Feixa Llarga s/n. Hospitalet de Llobregat, 08907 Barcelona, Spain, and the Bellvitge Biomedical Research Institute, Gran Via de l'Hospitalet, 199-203, L'Hospitalet de Llobregat, Barcelona, 08908 Barcelona, Spain solsona@ub.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holmgren</LastName><ForeName>Arne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>From the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden, arne.holmgren@ki.se.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>PDB</DataBankName><AccessionNumberList><AccessionNumber>2C9V</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate 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PubStatus="received"><Year>2015</Year><Month>12</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>6</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>6</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>5</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27261461</ArticleId><ArticleId IdType="pii">M115.708230</ArticleId><ArticleId IdType="doi">10.1074/jbc.M115.708230</ArticleId><ArticleId IdType="pmc">PMC5016121</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1392-7</Citation><ArticleIdList><ArticleId IdType="pubmed">19171884</ArticleId></ArticleIdList></Reference><Reference><Citation>Hum Mol Genet. 2003 Nov 1;12 (21):2753-64</Citation><ArticleIdList><ArticleId IdType="pubmed">12966034</ArticleId></ArticleIdList></Reference><Reference><Citation>J Mol Biol. 2002 Nov 22;324(2):247-56</Citation><ArticleIdList><ArticleId IdType="pubmed">12441104</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Struct Biol. 2003 Jun;10 (6):461-7</Citation><ArticleIdList><ArticleId IdType="pubmed">12754496</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18663-8</Citation><ArticleIdList><ArticleId IdType="pubmed">19022905</ArticleId></ArticleIdList></Reference><Reference><Citation>Antioxid Redox Signal. 2014 Jul 20;21(3):457-70</Citation><ArticleIdList><ArticleId IdType="pubmed">24483600</ArticleId></ArticleIdList></Reference><Reference><Citation>Antioxid Redox Signal. 2012 Dec 15;17(12):1738-47</Citation><ArticleIdList><ArticleId IdType="pubmed">22530689</ArticleId></ArticleIdList></Reference><Reference><Citation>J Cell Biol. 2009 Dec 14;187(6):761-72</Citation><ArticleIdList><ArticleId IdType="pubmed">19951898</ArticleId></ArticleIdList></Reference><Reference><Citation>Free Radic Biol Med. 2009 Jan 15;46(2):202-11</Citation><ArticleIdList><ArticleId IdType="pubmed">18996185</ArticleId></ArticleIdList></Reference><Reference><Citation>J Neurochem. 2012 May;121(3):475-85</Citation><ArticleIdList><ArticleId IdType="pubmed">22332887</ArticleId></ArticleIdList></Reference><Reference><Citation>Brain. 2006 Feb;129(Pt 2):451-64</Citation><ArticleIdList><ArticleId IdType="pubmed">16330499</ArticleId></ArticleIdList></Reference><Reference><Citation>Free Radic Biol Med. 2014 Jan;66:75-87</Citation><ArticleIdList><ArticleId IdType="pubmed">23899494</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2003 Feb 21;278(8):5984-92</Citation><ArticleIdList><ArticleId IdType="pubmed">12458194</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2006 May 2;103(18):7148-53</Citation><ArticleIdList><ArticleId IdType="pubmed">16636274</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 1993 Mar 4;362(6415):59-62</Citation><ArticleIdList><ArticleId IdType="pubmed">8446170</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Neurosci. 2010 Nov;13(11):1396-403</Citation><ArticleIdList><ArticleId IdType="pubmed">20953194</ArticleId></ArticleIdList></Reference><Reference><Citation>Acta Neuropathol. 2004 Feb;107(2):149-58</Citation><ArticleIdList><ArticleId IdType="pubmed">14648077</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2009 Oct 2;284(40):27746-58</Citation><ArticleIdList><ArticleId IdType="pubmed">19651777</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2005 Aug 19;280(33):29771-9</Citation><ArticleIdList><ArticleId IdType="pubmed">15958382</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2014 Sep 26;289(39):26722-32</Citation><ArticleIdList><ArticleId IdType="pubmed">25096579</ArticleId></ArticleIdList></Reference><Reference><Citation>Free Radic Biol Med. 2010 Mar 1;48(5):629-41</Citation><ArticleIdList><ArticleId IdType="pubmed">19969067</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2006 May 2;103(18):7142-7</Citation><ArticleIdList><ArticleId IdType="pubmed">16636275</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2012;7(10 ):e47838</Citation><ArticleIdList><ArticleId IdType="pubmed">23118898</ArticleId></ArticleIdList></Reference><Reference><Citation>Antioxid Redox Signal. 2009 Jul;11(7):1603-14</Citation><ArticleIdList><ArticleId IdType="pubmed">19271992</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochemistry. 2011 Aug 16;50(32):7057-66</Citation><ArticleIdList><ArticleId IdType="pubmed">21739997</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem J. 2012 Aug 15;446(1):59-67</Citation><ArticleIdList><ArticleId IdType="pubmed">22651090</ArticleId></ArticleIdList></Reference><Reference><Citation>Annu Rev Biochem. 2005;74:563-93</Citation><ArticleIdList><ArticleId IdType="pubmed">15952898</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2012 Nov 2;287(45):38210-9</Citation><ArticleIdList><ArticleId IdType="pubmed">22977247</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2011 Mar 12;377(9769):942-55</Citation><ArticleIdList><ArticleId IdType="pubmed">21296405</ArticleId></ArticleIdList></Reference><Reference><Citation>Ann Neurol. 1997 Feb;41(2):210-21</Citation><ArticleIdList><ArticleId IdType="pubmed">9029070</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 1989 Aug 25;264(24):13963-6</Citation><ArticleIdList><ArticleId IdType="pubmed">2668278</ArticleId></ArticleIdList></Reference><Reference><Citation>Neurodegener Dis. 2005;2(3-4):115-27</Citation><ArticleIdList><ArticleId IdType="pubmed">16909016</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2013 Feb 15;288(7):4970-80</Citation><ArticleIdList><ArticleId IdType="pubmed">23264618</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2006 Sep 29;281(39):28648-56</Citation><ArticleIdList><ArticleId IdType="pubmed">16880213</ArticleId></ArticleIdList></Reference><Reference><Citation>Exp Biol Med (Maywood). 2009 Oct;234(10):1140-54</Citation><ArticleIdList><ArticleId IdType="pubmed">19596823</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12066-71</Citation><ArticleIdList><ArticleId IdType="pubmed">23818595</ArticleId></ArticleIdList></Reference><Reference><Citation>EMBO J. 2004 Jul 21;23(14):2872-81</Citation><ArticleIdList><ArticleId IdType="pubmed">15215895</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2015 Dec 18;290(51):30624-36</Citation><ArticleIdList><ArticleId IdType="pubmed">26511321</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2007 Sep 21;282(38):28087-95</Citation><ArticleIdList><ArticleId IdType="pubmed">17666395</ArticleId></ArticleIdList></Reference><Reference><Citation>Hum Mol Genet. 2015 Jun 15;24(12 ):3427-39</Citation><ArticleIdList><ArticleId IdType="pubmed">25762155</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2008 Jan 11;283(2):866-74</Citation><ArticleIdList><ArticleId IdType="pubmed">18006498</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Neurol. 2011 Nov;7(11):616-30</Citation><ArticleIdList><ArticleId IdType="pubmed">22051914</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet Neurol. 2013 Mar;12(3):310-22</Citation><ArticleIdList><ArticleId IdType="pubmed">23415570</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochemistry. 2000 Jul 18;39(28):8125-32</Citation><ArticleIdList><ArticleId IdType="pubmed">10889018</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Biophys Res Commun. 2015 Aug 7;463(4):1196-202</Citation><ArticleIdList><ArticleId IdType="pubmed">26086102</ArticleId></ArticleIdList></Reference><Reference><Citation>J Neurochem. 2006 Mar;96(5):1277-88</Citation><ArticleIdList><ArticleId IdType="pubmed">16441516</ArticleId></ArticleIdList></Reference><Reference><Citation>Hum Mol Genet. 2010 Nov 15;19(22):4529-42</Citation><ArticleIdList><ArticleId IdType="pubmed">20829229</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5976-81</Citation><ArticleIdList><ArticleId IdType="pubmed">15056757</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2003 Jun 6;278(23):21032-9</Citation><ArticleIdList><ArticleId IdType="pubmed">12649272</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2008 Aug 29;283(35):24167-76</Citation><ArticleIdList><ArticleId IdType="pubmed">18552350</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 1994 Jun 17;264(5166):1772-5</Citation><ArticleIdList><ArticleId IdType="pubmed">8209258</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2009 May 15;284(20):13940-7</Citation><ArticleIdList><ArticleId IdType="pubmed">19299510</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2000 Nov 7;97(23 ):12571-6</Citation><ArticleIdList><ArticleId IdType="pubmed">11050163</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2008 May 16;283(20):13528-37</Citation><ArticleIdList><ArticleId IdType="pubmed">18316367</ArticleId></ArticleIdList></Reference><Reference><Citation>Free Radic Biol Med. 1995 Dec;19(6):741-8</Citation><ArticleIdList><ArticleId IdType="pubmed">8582646</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2001 Apr 20;276(16):12791-6</Citation><ArticleIdList><ArticleId IdType="pubmed">11278741</ArticleId></ArticleIdList></Reference><Reference><Citation>Expert Rev Mol Med. 2006 May 24;8(11):1-22</Citation><ArticleIdList><ArticleId IdType="pubmed">16723044</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Espagne</li><li>République populaire de Chine</li><li>Suède</li><li>États-Unis</li></country><region><li>Catalogne</li><li>Svealand</li></region><settlement><li>Stockholm</li></settlement></list><tree><country name="Espagne"><region name="Catalogne"><name sortKey="Alvarez Zaldiernas, Cristina" sort="Alvarez Zaldiernas, Cristina" uniqKey="Alvarez Zaldiernas C" first="Cristina" last="Álvarez-Zaldiernas">Cristina Álvarez-Zaldiernas</name></region><name sortKey="Blasi, Juan" sort="Blasi, Juan" uniqKey="Blasi J" first="Juan" last="Blasi">Juan Blasi</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Lu, Jun" sort="Lu, Jun" uniqKey="Lu J" first="Jun" last="Lu">Jun Lu</name></noRegion></country><country name="Suède"><region name="Svealand"><name sortKey="Zheng, Yujuan" sort="Zheng, Yujuan" uniqKey="Zheng Y" first="Yujuan" last="Zheng">Yujuan Zheng</name></region><name sortKey="Holmgren, Arne" sort="Holmgren, Arne" uniqKey="Holmgren A" first="Arne" last="Holmgren">Arne Holmgren</name><name sortKey="Yang, Hongqian" sort="Yang, Hongqian" uniqKey="Yang H" first="Hongqian" last="Yang">Hongqian Yang</name></country><country name="États-Unis"><noRegion><name sortKey="Solsona, Carles" sort="Solsona, Carles" uniqKey="Solsona C" first="Carles" last="Solsona">Carles Solsona</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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