The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease
Identifieur interne : 000453 ( Main/Corpus ); précédent : 000452; suivant : 000454The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease
Auteurs : Tianhong Pan ; Seiji Kondo ; Weidong Le ; Joseph JankovicSource :
- Brain [ 0006-8950 ] ; 2008-08.
Abstract
The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of α-synuclein and the increase of intracellular concentrations of non-mutant α-synuclein have been associated with Parkinson's disease phenotype. The demonstration that α-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant α-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.
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DOI: 10.1093/brain/awm318
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Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: josephj@bcm.tmc.edu</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2008-08">2008-08</date><biblScope unit="volume">131</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1969">1969</biblScope><biblScope unit="page" to="1978">1978</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">F92CEB1DBB9F75DC8E028D95F46C52FAB93DCD3D</idno><idno type="DOI">10.1093/brain/awm318</idno><idno type="ArticleID">awm318</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of α-synuclein and the increase of intracellular concentrations of non-mutant α-synuclein have been associated with Parkinson's disease phenotype. The demonstration that α-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant α-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Tianhong Pan</name><affiliations><json:string>Parkinson's Disease Research Laboratory, Baylor College of Medicine, 2Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and 3Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</json:string></affiliations></json:item><json:item><name>Seiji Kondo</name><affiliations><json:string>Parkinson's Disease Research Laboratory, Baylor College of Medicine, 2Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and 3Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</json:string></affiliations></json:item><json:item><name>Weidong Le</name><affiliations><json:string>Parkinson's Disease Research Laboratory, Baylor College of Medicine, 2Department of Neurosurgery, University of Texas M. D. 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The fact that mutant α-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. 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D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation></author><author><persName><forename type="first">Seiji</forename><surname>Kondo</surname></persName><affiliation>Parkinson's Disease Research Laboratory, Baylor College of Medicine, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation></author><author><persName><forename type="first">Weidong</forename><surname>Le</surname></persName><affiliation>Parkinson's Disease Research Laboratory, Baylor College of Medicine, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation></author><author corresp="yes"><persName><forename type="first">Joseph</forename><surname>Jankovic</surname></persName><email>josephj@bcm.tmc.edu</email><affiliation>Parkinson's Disease Research Laboratory, Baylor College of Medicine, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation></author></analytic><monogr><title level="j">Brain</title><idno type="pISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2008-08"></date><biblScope unit="volume">131</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1969">1969</biblScope><biblScope unit="page" to="1978">1978</biblScope></imprint></monogr><idno type="istex">F92CEB1DBB9F75DC8E028D95F46C52FAB93DCD3D</idno><idno type="DOI">10.1093/brain/awm318</idno><idno type="ArticleID">awm318</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2008-01-10</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of α-synuclein and the increase of intracellular concentrations of non-mutant α-synuclein have been associated with Parkinson's disease phenotype. The demonstration that α-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant α-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.</p></abstract><textClass><keywords scheme="keyword"><list><item><term>Review Article</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>autophagy-lysosome pathway</term></item><item><term>neurodegenerative disease</term></item><item><term>neuroprotection</term></item><item><term>Parkinson's disease</term></item><item><term>ubiquitin-proteasome system</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-01-10">Created</change><change when="2008-08">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/F92CEB1DBB9F75DC8E028D95F46C52FAB93DCD3D/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="review-article"><front><journal-meta><journal-id journal-id-type="hwp">brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-title>Brain</journal-title><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/brain/awm318</article-id><article-id pub-id-type="publisher-id">awm318</article-id><article-categories><subj-group><subject>Review Article</subject></subj-group></article-categories><title-group><article-title>The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Pan</surname><given-names>Tianhong</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kondo</surname><given-names>Seiji</given-names></name><xref ref-type="aff" rid="AFF1"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Le</surname><given-names>Weidong</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Jankovic</surname><given-names>Joseph</given-names></name><xref ref-type="aff" rid="AFF1"><sup>3</sup></xref></contrib></contrib-group><aff id="AFF1"><sup>1</sup>Parkinson's Disease Research Laboratory, Baylor College of Medicine, <sup>2</sup>Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and <sup>3</sup>Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</aff><author-notes><corresp>Correspondence to: Joseph Jankovic, MD, Professor of Neurology, Director, Parkinson's Disease Center, and Movement Disorders Clinic, Baylor College of Medicine, Department of Neurology, 6550 Fannin #1801Houston, TX 77030, USA. E-mail: <email>josephj@bcm.tmc.edu</email></corresp></author-notes><pub-date pub-type="ppub"><month>8</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>10</day><month>1</month><year>2008</year></pub-date><volume>131</volume><issue>8</issue><fpage>1969</fpage><lpage>1978</lpage><history><date date-type="received"><day>24</day><month>7</month><year>2007</year></date><date date-type="rev-recd"><day>19</day><month>10</month><year>2007</year></date><date date-type="accepted"><day>11</day><month>12</month><year>2007</year></date></history><permissions><copyright-statement>© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2008</copyright-year></permissions><abstract><p>The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of α-synuclein and the increase of intracellular concentrations of non-mutant α-synuclein have been associated with Parkinson's disease phenotype. The demonstration that α-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant α-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.</p></abstract><kwd-group><kwd>autophagy-lysosome pathway</kwd><kwd>neurodegenerative disease</kwd><kwd>neuroprotection</kwd><kwd>Parkinson's disease</kwd><kwd>ubiquitin-proteasome system</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Tianhong</namePart><namePart type="family">Pan</namePart><affiliation>Parkinson's Disease Research Laboratory, Baylor College of Medicine, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Seiji</namePart><namePart type="family">Kondo</namePart><affiliation>Parkinson's Disease Research Laboratory, Baylor College of Medicine, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Weidong</namePart><namePart type="family">Le</namePart><affiliation>Parkinson's Disease Research Laboratory, Baylor College of Medicine, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Joseph</namePart><namePart type="family">Jankovic</namePart><affiliation>Parkinson's Disease Research Laboratory, Baylor College of Medicine, Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center and Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</affiliation><affiliation>E-mail: josephj@bcm.tmc.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="review-article"></genre><subject><topic>Review Article</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2008-08</dateIssued><dateCreated encoding="w3cdtf">2008-01-10</dateCreated><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of α-synuclein and the increase of intracellular concentrations of non-mutant α-synuclein have been associated with Parkinson's disease phenotype. The demonstration that α-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant α-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.</abstract><subject><genre>Keywords</genre><topic>autophagy-lysosome pathway</topic><topic>neurodegenerative disease</topic><topic>neuroprotection</topic><topic>Parkinson's disease</topic><topic>ubiquitin-proteasome system</topic></subject><relatedItem type="host"><titleInfo><title>Brain</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0006-8950</identifier><identifier type="eISSN">1460-2156</identifier><identifier type="PublisherID">brainj</identifier><identifier type="PublisherID-hwp">brain</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>131</number></detail><detail type="issue"><caption>no.</caption><number>8</number></detail><extent unit="pages"><start>1969</start><end>1978</end></extent></part></relatedItem><identifier type="istex">F92CEB1DBB9F75DC8E028D95F46C52FAB93DCD3D</identifier><identifier type="DOI">10.1093/brain/awm318</identifier><identifier type="ArticleID">awm318</identifier><accessCondition type="use and reproduction" contentType="copyright">© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. 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