The Cast of Molecular Characters in Parkinson's Disease
Identifieur interne : 002373 ( Main/Corpus ); précédent : 002372; suivant : 002374The Cast of Molecular Characters in Parkinson's Disease
Auteurs : Kah Leong Lim ; Valina L. Dawson ; Ted M. DawsonSource :
- Annals of the New York Academy of SciencesPARKINSON'S DISEASE: The Life Cycle of the Dopamine Neuron [ 0077-8923 ] ; 2003-06.
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Abstract
Abstract: Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.
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DOI: 10.1111/j.1749-6632.2003.tb07465.x
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Dawson</name><affiliation><mods:affiliation>Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</mods:affiliation></affiliation></author><author><name sortKey="Dawson, Ted M" sort="Dawson, Ted M" uniqKey="Dawson T" first="Ted M." last="Dawson">Ted M. 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Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>KAH LEONG LIM</name><affiliations><json:string>Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433</json:string></affiliations></json:item><json:item><name>VALINA L. DAWSON</name><affiliations><json:string>Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</json:string><json:string>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</json:string><json:string>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</json:string><json:string>Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</json:string></affiliations></json:item><json:item><name>TED M. 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Dawson, M.D., Ph.D., Institute for Cell Engineering, Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Carnegie 214, Baltimore, MD 21287. Voice: 410‐614‐3359; fax: 410‐614‐9568.</p></note><affiliation>Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><affiliation>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><affiliation>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation></author></analytic><monogr><title level="j">Annals of the New York Academy of SciencesPARKINSON'S DISEASE: The Life Cycle of the Dopamine Neuron</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="2003-06"></date><biblScope unit="volume">991</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="80">80</biblScope><biblScope unit="page" to="92">92</biblScope></imprint></monogr><idno type="istex">178BBD878FE4A1A4E036E25B6805E0924A46334B</idno><idno type="DOI">10.1111/j.1749-6632.2003.tb07465.x</idno><idno type="ArticleID">NYAS80</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2003</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>α‐synuclein</term></item><item><term>parkin</term></item><item><term>UCHL1</term></item><item><term>ubiquitin‐proteasome system</term></item><item><term>ubiquitination</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2003-06">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/178BBD878FE4A1A4E036E25B6805E0924A46334B/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="06001"><doi origin="wiley">10.1111/nyas.2003.991.issue-1</doi><titleGroup><title type="main">PARKINSON'S DISEASE: The Life Cycle of the Dopamine Neuron</title></titleGroup><numberingGroup><numbering type="journalVolume" number="991">991</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2003-06">June 2003</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="9" status="forIssue"><doi origin="wiley">10.1111/j.1749-6632.2003.tb07465.x</doi><idGroup><id type="unit" value="NYAS80"></id></idGroup><countGroup><count type="pageTotal" number="13"></count></countGroup><titleGroup><title type="tocHeading1">Parkinson's Disease: The Life Cycle of the Dopamine Neuron: Part III. From Molecules to Organism: The Molecules</title></titleGroup><eventGroup><event type="firstOnline" date="2006-01-24"></event><event type="publishedOnlineFinalForm" date="2006-01-24"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.5 mode:FullText source:FullText result:FullText" date="2010-04-09"></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="80">80</numbering><numbering type="pageLast" number="92">92</numbering></numberingGroup><correspondenceTo>Address for correspondence: Ted M. Dawson, M.D., Ph.D., Institute for Cell Engineering, Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Carnegie 214, Baltimore, MD 21287. Voice: 410‐614‐3359; fax: 410‐614‐9568. <email>tdawson@jhmi.edu</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:NYAS.NYAS80.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="59"></count><count type="linksCrossRef" number="79"></count></countGroup><titleGroup><title type="main">The Cast of Molecular Characters in Parkinson's Disease</title><title type="subtitle">Felons, Conspirators, and Suspects</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>KAH LEONG</givenNames><familyName>LIM</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a2 #a3 #a4 #a5"><personName><givenNames>VALINA L.</givenNames><familyName>DAWSON</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a2 #a3 #a4" corresponding="yes"><personName><givenNames>TED M.</givenNames><familyName>DAWSON</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="SG"><unparsedAffiliation>Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="US"><unparsedAffiliation>Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="US"><unparsedAffiliation>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</unparsedAffiliation></affiliation><affiliation xml:id="a4" countryCode="US"><unparsedAffiliation>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</unparsedAffiliation></affiliation><affiliation xml:id="a5" countryCode="US"><unparsedAffiliation>Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">Parkinson's disease</keyword><keyword xml:id="k2">α‐synuclein</keyword><keyword xml:id="k3">parkin</keyword><keyword xml:id="k4">UCHL1</keyword><keyword xml:id="k5">ubiquitin‐proteasome system</keyword><keyword xml:id="k6">ubiquitination</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>A<sc>bstract</sc>: </b> Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The Cast of Molecular Characters in Parkinson's Disease</title><subTitle>Felons, Conspirators, and Suspects</subTitle></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>The Cast of Molecular Characters in Parkinson's Disease</title></titleInfo><name type="personal"><namePart type="given">KAH LEONG</namePart><namePart type="family">LIM</namePart><affiliation>Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">VALINA L.</namePart><namePart type="family">DAWSON</namePart><affiliation>Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><affiliation>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><affiliation>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><affiliation>Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">TED M.</namePart><namePart type="family">DAWSON</namePart><affiliation>Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><affiliation>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><affiliation>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA</affiliation><description>Correspondence: Address for correspondence: Ted M. Dawson, M.D., Ph.D., Institute for Cell Engineering, Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Carnegie 214, Baltimore, MD 21287. Voice: 410‐614‐3359; fax: 410‐614‐9568. </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">2003-06</dateIssued><copyrightDate encoding="w3cdtf">2003</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">59</extent></physicalDescription><abstract lang="en">Abstract: Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.</abstract><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>α‐synuclein</topic><topic>parkin</topic><topic>UCHL1</topic><topic>ubiquitin‐proteasome system</topic><topic>ubiquitination</topic></subject><relatedItem type="host"><titleInfo><title>Annals of the New York Academy of SciencesPARKINSON'S DISEASE: The Life Cycle of the Dopamine Neuron</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>2003</date><detail type="volume"><caption>vol.</caption><number>991</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>80</start><end>92</end><total>13</total></extent></part></relatedItem><identifier type="istex">178BBD878FE4A1A4E036E25B6805E0924A46334B</identifier><identifier type="DOI">10.1111/j.1749-6632.2003.tb07465.x</identifier><identifier type="ArticleID">NYAS80</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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