HO-1-mediated macroautophagy : a mechanism for unregulated iron deposition in aging and degenerating neural tissues
Identifieur interne : 000465 ( PascalFrancis/Checkpoint ); précédent : 000464; suivant : 000466HO-1-mediated macroautophagy : a mechanism for unregulated iron deposition in aging and degenerating neural tissues
Auteurs : Hillel Zukor [Canada] ; WEI SONG [Canada] ; Adrienne Liberman [Canada] ; JEANNIE MUI [Canada] ; Hojatollah Vali [Canada] ; Carine Fillebeen [Canada] ; Kostas Pantopoulos [Canada] ; Ting-Di Wu [France] ; Jean-Luc Guerquin-Kern [France] ; Hyman M. Schipper [Canada]Source :
- Journal of neurochemistry [ 0022-3042 ] ; 2009.
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Abstract
Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.
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Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Neurology and Neurosurgery and Department of Medicine, Division of Geriatrics, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Wei Song" sort="Wei Song" uniqKey="Wei Song" last="Wei Song">WEI SONG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre for Neurotranslational Research, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Liberman, Adrienne" sort="Liberman, Adrienne" uniqKey="Liberman A" first="Adrienne" last="Liberman">Adrienne Liberman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre for Neurotranslational Research, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Jeannie Mui" sort="Jeannie Mui" uniqKey="Jeannie Mui" last="Jeannie Mui">JEANNIE MUI</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Facility for Electron Microscopy Research, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Vali, Hojatollah" sort="Vali, Hojatollah" uniqKey="Vali H" first="Hojatollah" last="Vali">Hojatollah Vali</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Facility for Electron Microscopy Research, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Faculty of Dentistry, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Fillebeen, Carine" sort="Fillebeen, Carine" uniqKey="Fillebeen C" first="Carine" last="Fillebeen">Carine Fillebeen</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Pantopoulos, Kostas" sort="Pantopoulos, Kostas" uniqKey="Pantopoulos K" first="Kostas" last="Pantopoulos">Kostas Pantopoulos</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Department of Microbiology and Immunology and Division of Experimental Medicine, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Wu, Ting Di" sort="Wu, Ting Di" uniqKey="Wu T" first="Ting-Di" last="Wu">Ting-Di Wu</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>INSERM, U759</s1><s2>Orsay</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Orsay</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Institut Curie, Laboratoire de Microscopic Ionique</s1><s2>Orsay</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Guerquin Kern, Jean Luc" sort="Guerquin Kern, Jean Luc" uniqKey="Guerquin Kern J" first="Jean-Luc" last="Guerquin-Kern">Jean-Luc Guerquin-Kern</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>INSERM, U759</s1><s2>Orsay</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Orsay</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Institut Curie, Laboratoire de Microscopic Ionique</s1><s2>Orsay</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre for Neurotranslational Research, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Neurology and Neurosurgery and Department of Medicine, Division of Geriatrics, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of neurochemistry</title><title level="j" type="abbreviated">J. neurochem.</title><idno type="ISSN">0022-3042</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alzheimer disease</term><term>Cerebral disorder</term><term>Dynamics</term><term>Encephalon</term><term>Heme</term><term>Human</term><term>Ions</term><term>Iron</term><term>Mass spectrometry</term><term>Mitochondria</term><term>Morphology</term><term>Oxidative stress</term><term>Parkinson disease</term><term>Technique</term><term>Transferrin</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Fer</term><term>Stress oxydatif</term><term>Transferrine</term><term>Mitochondrie</term><term>Maladie de Parkinson</term><term>Hème</term><term>Encéphale</term><term>Dynamique</term><term>Pathologie de l'encéphale</term><term>Ion</term><term>Spectrométrie masse</term><term>Démence d'Alzheimer</term><term>Technique</term><term>Morphologie</term><term>Homme</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Fer</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-3042</s0></fA01><fA02 i1="01"><s0>JONRA9</s0></fA02><fA03 i2="1"><s0>J. neurochem.</s0></fA03><fA05><s2>109</s2></fA05><fA06><s2>3</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>HO-1-mediated macroautophagy : a mechanism for unregulated iron deposition in aging and degenerating neural tissues</s1></fA08><fA11 i1="01" i2="1"><s1>ZUKOR (Hillel)</s1></fA11><fA11 i1="02" i2="1"><s1>WEI SONG</s1></fA11><fA11 i1="03" i2="1"><s1>LIBERMAN (Adrienne)</s1></fA11><fA11 i1="04" i2="1"><s1>JEANNIE MUI</s1></fA11><fA11 i1="05" i2="1"><s1>VALI (Hojatollah)</s1></fA11><fA11 i1="06" i2="1"><s1>FILLEBEEN (Carine)</s1></fA11><fA11 i1="07" i2="1"><s1>PANTOPOULOS (Kostas)</s1></fA11><fA11 i1="08" i2="1"><s1>WU (Ting-Di)</s1></fA11><fA11 i1="09" i2="1"><s1>GUERQUIN-KERN (Jean-Luc)</s1></fA11><fA11 i1="10" i2="1"><s1>SCHIPPER (Hyman M.)</s1></fA11><fA14 i1="01"><s1>Centre for Neurotranslational Research, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Neurology and Neurosurgery and Department of Medicine, Division of Geriatrics, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="03"><s1>Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="05"><s1>Facility for Electron Microscopy Research, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Faculty of Dentistry, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>5 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Microbiology and Immunology and Division of Experimental Medicine, McGill University</s1><s2>Montreal, Quebec</s2><s3>CAN</s3><sZ>7 aut.</sZ></fA14><fA14 i1="08"><s1>INSERM, U759</s1><s2>Orsay</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="09"><s1>Institut Curie, Laboratoire de Microscopic Ionique</s1><s2>Orsay</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></fA14><fA20><s1>776-791</s1></fA20><fA21><s1>2009</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>4037</s2><s5>354000186050310090</s5></fA43><fA44><s0>0000</s0><s1>© 2009 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>2 p.1/4</s0></fA45><fA47 i1="01" i2="1"><s0>09-0209855</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Journal of neurochemistry</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17G</s0></fC02><fC02 i1="02" i2="X"><s0>002B18C13</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Fer</s0><s2>NC</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Iron</s0><s2>NC</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Hierro</s0><s2>NC</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Stress oxydatif</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Oxidative stress</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Estrés oxidativo</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Transferrine</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Transferrin</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Transferrina</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Mitochondrie</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" 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l'encéphale</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>09</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Ion</s0><s2>NA</s2><s5>10</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Ions</s0><s2>NA</s2><s5>10</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Ión</s0><s2>NA</s2><s5>10</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Spectrométrie masse</s0><s5>11</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Mass spectrometry</s0><s5>11</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Espectrometría masa</s0><s5>11</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Démence d'Alzheimer</s0><s5>12</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Alzheimer disease</s0><s5>12</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Demencia Alzheimer</s0><s5>12</s5></fC03><fC03 i1="13" i2="X" l="FRE"><s0>Technique</s0><s5>13</s5></fC03><fC03 i1="13" i2="X" l="ENG"><s0>Technique</s0><s5>13</s5></fC03><fC03 i1="13" i2="X" 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i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>Canada</li><li>France</li></country><region><li>Québec</li></region><settlement><li>Montréal</li><li>Orsay</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Zukor, Hillel" sort="Zukor, Hillel" uniqKey="Zukor H" first="Hillel" last="Zukor">Hillel Zukor</name></noRegion><name sortKey="Fillebeen, Carine" sort="Fillebeen, Carine" uniqKey="Fillebeen C" first="Carine" last="Fillebeen">Carine Fillebeen</name><name sortKey="Jeannie Mui" sort="Jeannie Mui" uniqKey="Jeannie Mui" last="Jeannie Mui">JEANNIE MUI</name><name sortKey="Jeannie Mui" sort="Jeannie Mui" uniqKey="Jeannie Mui" last="Jeannie Mui">JEANNIE MUI</name><name sortKey="Liberman, Adrienne" sort="Liberman, Adrienne" uniqKey="Liberman A" first="Adrienne" last="Liberman">Adrienne Liberman</name><name sortKey="Liberman, Adrienne" sort="Liberman, Adrienne" uniqKey="Liberman A" first="Adrienne" last="Liberman">Adrienne Liberman</name><name sortKey="Pantopoulos, Kostas" sort="Pantopoulos, Kostas" uniqKey="Pantopoulos K" first="Kostas" last="Pantopoulos">Kostas Pantopoulos</name><name sortKey="Pantopoulos, Kostas" sort="Pantopoulos, Kostas" uniqKey="Pantopoulos K" first="Kostas" last="Pantopoulos">Kostas Pantopoulos</name><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name><name sortKey="Schipper, Hyman M" sort="Schipper, Hyman M" uniqKey="Schipper H" first="Hyman M." last="Schipper">Hyman M. Schipper</name><name sortKey="Vali, Hojatollah" sort="Vali, Hojatollah" uniqKey="Vali H" first="Hojatollah" last="Vali">Hojatollah Vali</name><name sortKey="Vali, Hojatollah" sort="Vali, Hojatollah" uniqKey="Vali H" first="Hojatollah" last="Vali">Hojatollah Vali</name><name sortKey="Vali, Hojatollah" sort="Vali, Hojatollah" uniqKey="Vali H" first="Hojatollah" last="Vali">Hojatollah Vali</name><name sortKey="Wei Song" sort="Wei Song" uniqKey="Wei Song" last="Wei Song">WEI SONG</name><name sortKey="Wei Song" sort="Wei Song" uniqKey="Wei Song" last="Wei Song">WEI SONG</name><name sortKey="Zukor, Hillel" sort="Zukor, Hillel" uniqKey="Zukor H" first="Hillel" last="Zukor">Hillel Zukor</name><name sortKey="Zukor, Hillel" sort="Zukor, Hillel" uniqKey="Zukor H" first="Hillel" last="Zukor">Hillel Zukor</name></country><country name="France"><noRegion><name sortKey="Wu, Ting Di" sort="Wu, Ting Di" uniqKey="Wu T" first="Ting-Di" last="Wu">Ting-Di Wu</name></noRegion><name sortKey="Guerquin Kern, Jean Luc" sort="Guerquin Kern, Jean Luc" uniqKey="Guerquin Kern J" first="Jean-Luc" last="Guerquin-Kern">Jean-Luc Guerquin-Kern</name><name sortKey="Guerquin Kern, Jean Luc" sort="Guerquin Kern, Jean Luc" uniqKey="Guerquin Kern J" first="Jean-Luc" last="Guerquin-Kern">Jean-Luc Guerquin-Kern</name><name sortKey="Wu, Ting Di" sort="Wu, Ting Di" uniqKey="Wu T" first="Ting-Di" last="Wu">Ting-Di Wu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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