Inflammation and the Degenerative Diseases of Aging
Identifieur interne : 002118 ( Main/Corpus ); précédent : 002117; suivant : 002119Inflammation and the Degenerative Diseases of Aging
Auteurs : Patrick L. Mcgeer ; Edith G. McgeerSource :
- Annals of the New York Academy of SciencesProtective Strategies for Neurodegenerative Diseases [ 0077-8923 ] ; 2004-12.
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Abstract
Abstract: Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson‐dementia complex of Guam, all of the tauopathies, and age‐related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two‐edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte‐directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue‐based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti‐inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti‐inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti‐inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti‐inflammatory agents, are needed to achieve the suggested neurological benefits.
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DOI: 10.1196/annals.1332.007
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inflammation and the Degenerative Diseases of Aging</title><author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L." last="Mcgeer">Patrick L. Mcgeer</name><affiliation><mods:affiliation>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Mcgeer, Edith G" sort="Mcgeer, Edith G" uniqKey="Mcgeer E" first="Edith G." last="Mcgeer">Edith G. 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Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson‐dementia complex of Guam, all of the tauopathies, and age‐related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two‐edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte‐directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue‐based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti‐inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti‐inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti‐inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti‐inflammatory agents, are needed to achieve the suggested neurological benefits.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>PATRICK L. McGEER</name><affiliations><json:string>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada</json:string></affiliations></json:item><json:item><name>EDITH G. McGEER</name><affiliations><json:string>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Alzheimer's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>amyotrophic lateral sclerosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>tauopathies</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>osteoarthritis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>rheumatoid arthritis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>atherosclerosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>myocardial infarction</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NSAIDs</value></json:item></subject><articleId><json:string>NYAS104</json:string></articleId><language><json:string>eng</json:string></language><abstract>Abstract: Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson‐dementia complex of Guam, all of the tauopathies, and age‐related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two‐edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte‐directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue‐based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti‐inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti‐inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti‐inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. 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McGeer, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada. Voice: 604‐822‐7380; fax: 604‐822‐7086.</p></note><affiliation>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada</affiliation></author></analytic><monogr><title level="j">Annals of the New York Academy of SciencesProtective Strategies for Neurodegenerative Diseases</title><idno type="pISSN">0077-8923</idno><idno type="eISSN">1749-6632</idno><idno type="DOI">10.1111/(ISSN)1749-6632</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2004-12"></date><biblScope unit="volume">1035</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="104">104</biblScope><biblScope unit="page" to="116">116</biblScope></imprint></monogr><idno type="istex">206EE1776C1F24C6DA9DFA709C3D363A5967BA6C</idno><idno type="DOI">10.1196/annals.1332.007</idno><idno type="ArticleID">NYAS104</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2004</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson‐dementia complex of Guam, all of the tauopathies, and age‐related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two‐edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte‐directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue‐based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti‐inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti‐inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti‐inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti‐inflammatory agents, are needed to achieve the suggested neurological benefits.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Alzheimer's disease</term></item><item><term>Parkinson's disease</term></item><item><term>amyotrophic lateral sclerosis</term></item><item><term>tauopathies</term></item><item><term>osteoarthritis</term></item><item><term>rheumatoid arthritis</term></item><item><term>atherosclerosis</term></item><item><term>myocardial infarction</term></item><item><term>NSAIDs</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2004-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/206EE1776C1F24C6DA9DFA709C3D363A5967BA6C/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1749-6632</doi><issn type="print">0077-8923</issn><issn type="electronic">1749-6632</issn><idGroup><id type="product" value="NYAS"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="ANNALS OF NEW YORK ACADEMY SCIENCES">Annals of the New York Academy of Sciences</title></titleGroup></publicationMeta><publicationMeta level="part" position="12001"><doi origin="wiley">10.1111/nyas.2004.1035.issue-1</doi><titleGroup><title type="main">Protective Strategies for Neurodegenerative Diseases</title></titleGroup><numberingGroup><numbering type="journalVolume" number="1035">1035</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2004-12">December 2004</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="8" status="forIssue"><doi origin="wiley">10.1196/annals.1332.007</doi><idGroup><id type="unit" value="NYAS104"></id></idGroup><countGroup><count type="pageTotal" number="13"></count></countGroup><titleGroup><title type="tocHeading1">Protective Strategies for Neurodegenerative Diseases</title></titleGroup><eventGroup><event type="firstOnline" date="2006-01-12"></event><event type="publishedOnlineFinalForm" date="2006-01-12"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-02-27"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-19"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="104">104</numbering><numbering type="pageLast" number="116">116</numbering></numberingGroup><correspondenceTo>Address for correspondence: Dr. Patrick L. McGeer, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada. Voice: 604‐822‐7380; fax: 604‐822‐7086. <email>mcgeerpl@interchange.ubc.ca</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:NYAS.NYAS104.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="1"></count><count type="tableTotal" number="1"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="86"></count><count type="linksCrossRef" number="84"></count></countGroup><titleGroup><title type="main">Inflammation and the Degenerative Diseases of Aging</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>PATRICK L.</givenNames><familyName>McGEER</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1" corresponding="yes"><personName><givenNames>EDITH G.</givenNames><familyName>McGEER</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="CA"><unparsedAffiliation>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">Alzheimer's disease</keyword><keyword xml:id="k2">Parkinson's disease</keyword><keyword xml:id="k3">amyotrophic lateral sclerosis</keyword><keyword xml:id="k4">tauopathies</keyword><keyword xml:id="k5">osteoarthritis</keyword><keyword xml:id="k6">rheumatoid arthritis</keyword><keyword xml:id="k7">atherosclerosis</keyword><keyword xml:id="k8">myocardial infarction</keyword><keyword xml:id="k9">NSAIDs</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>A<sc>bstract</sc>: </b> Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson‐dementia complex of Guam, all of the tauopathies, and age‐related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two‐edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte‐directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue‐based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti‐inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti‐inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti‐inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti‐inflammatory agents, are needed to achieve the suggested neurological benefits.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Inflammation and the Degenerative Diseases of Aging</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Inflammation and the Degenerative Diseases of Aging</title></titleInfo><name type="personal"><namePart type="given">PATRICK L.</namePart><namePart type="family">McGEER</namePart><affiliation>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">EDITH G.</namePart><namePart type="family">McGEER</namePart><affiliation>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><description>Correspondence: Address for correspondence: Dr. Patrick L. McGeer, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada. Voice: 604‐822‐7380; fax: 604‐822‐7086. </description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2004-12</dateIssued><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">1</extent><extent unit="tables">1</extent><extent unit="references">86</extent></physicalDescription><abstract lang="en">Abstract: Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson‐dementia complex of Guam, all of the tauopathies, and age‐related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two‐edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte‐directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue‐based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti‐inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti‐inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti‐inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti‐inflammatory agents, are needed to achieve the suggested neurological benefits.</abstract><subject lang="en"><genre>Keywords</genre><topic>Alzheimer's disease</topic><topic>Parkinson's disease</topic><topic>amyotrophic lateral sclerosis</topic><topic>tauopathies</topic><topic>osteoarthritis</topic><topic>rheumatoid arthritis</topic><topic>atherosclerosis</topic><topic>myocardial infarction</topic><topic>NSAIDs</topic></subject><relatedItem type="host"><titleInfo><title>Annals of the New York Academy of SciencesProtective Strategies for Neurodegenerative Diseases</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0077-8923</identifier><identifier type="eISSN">1749-6632</identifier><identifier type="DOI">10.1111/(ISSN)1749-6632</identifier><identifier type="PublisherID">NYAS</identifier><part><date>2004</date><detail type="volume"><caption>vol.</caption><number>1035</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>104</start><end>116</end><total>13</total></extent></part></relatedItem><identifier type="istex">206EE1776C1F24C6DA9DFA709C3D363A5967BA6C</identifier><identifier type="DOI">10.1196/annals.1332.007</identifier><identifier type="ArticleID">NYAS104</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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