The genetics of Parkinson's disease: Progress and therapeutic implications
Identifieur interne : 000602 ( Istex/Corpus ); précédent : 000601; suivant : 000603The genetics of Parkinson's disease: Progress and therapeutic implications
Auteurs : Andrew B. Singleton ; Matthew J. Farrer ; Vincenzo BonifatiSource :
- Movement Disorders [ 0885-3185 ] ; 2013-01.
Abstract
The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease‐causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second‐generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha‐synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology‐based therapeutic approaches in this disease. © 2013 Movement Disorder Society
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DOI: 10.1002/mds.25249
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ISTEX:1897BB23048D40AB2FDCC914B29DCA3B9F6AD5ACLe document en format XML
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Farrer</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, Canada</mods:affiliation></affiliation></author><author><name sortKey="Bonifati, Vincenzo" sort="Bonifati, Vincenzo" uniqKey="Bonifati V" first="Vincenzo" last="Bonifati">Vincenzo Bonifati</name><affiliation><mods:affiliation>Department of Clinical Genetics, Rotterdam, Erasmus MC, The Netherlands</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1002/mds.25249</idno><idno type="url">https://api-v5.istex.fr/document/1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000602</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000602</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">The genetics of Parkinson's disease: Progress and therapeutic implications</title><author><name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name><affiliation><mods:affiliation>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Maryland, Bethesda, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: singleta@mail.nih.gov</mods:affiliation></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, Canada</mods:affiliation></affiliation></author><author><name sortKey="Bonifati, Vincenzo" sort="Bonifati, Vincenzo" uniqKey="Bonifati V" first="Vincenzo" last="Bonifati">Vincenzo Bonifati</name><affiliation><mods:affiliation>Department of Clinical Genetics, Rotterdam, Erasmus MC, The Netherlands</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov Disord</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-01">2013-01</date><biblScope unit="volume">28</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="14">14</biblScope><biblScope unit="page" to="23">23</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC</idno><idno type="DOI">10.1002/mds.25249</idno><idno type="ArticleID">MDS25249</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease‐causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second‐generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha‐synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology‐based therapeutic approaches in this disease. © 2013 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Andrew B. Singleton PhD</name><affiliations><json:string>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Maryland, Bethesda, USA</json:string><json:string>E-mail: singleta@mail.nih.gov</json:string></affiliations></json:item><json:item><name>Matthew J. Farrer PhD</name><affiliations><json:string>Department of Medical Genetics, University of British Columbia, Vancouver, Canada</json:string></affiliations></json:item><json:item><name>Vincenzo Bonifati MD, PhD</name><affiliations><json:string>Department of Clinical Genetics, Rotterdam, Erasmus MC, The Netherlands</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>genetics</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>therapeutics</value></json:item></subject><articleId><json:string>MDS25249</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>reviewArticle</json:string></originalGenre><abstract>The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease‐causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second‐generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha‐synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology‐based therapeutic approaches in this disease. © 2013 Movement Disorder Society</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 809.972 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1698</abstractCharCount><pdfWordCount>6960</pdfWordCount><pdfCharCount>44868</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>253</abstractWordCount></qualityIndicators><title>The genetics of Parkinson's disease: Progress and therapeutic implications</title><genre><json:string>review-article</json:string></genre><host><title>Movement Disorders</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi><issn><json:string>0885-3185</json:string></issn><eissn><json:string>1531-8257</json:string></eissn><publisherId><json:string>MDS</json:string></publisherId><volume>28</volume><issue>1</issue><pages><first>14</first><last>23</last><total>10</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Review</value></json:item></subject></host><categories><wos><json:string>science</json:string><json:string>clinical neurology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>neurology & neurosurgery</json:string></scienceMetrix></categories><publicationDate>2013</publicationDate><copyrightDate>2013</copyrightDate><doi><json:string>10.1002/mds.25249</json:string></doi><id>1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC</id><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api-v5.istex.fr/document/1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api-v5.istex.fr/document/1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api-v5.istex.fr/document/1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">The genetics of Parkinson's disease: Progress and therapeutic implications</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><availability><p>Copyright © 2013 Movement Disorder SocietyCopyright © 2013 Movement Disorders Society</p></availability><date>2013-01-17</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The genetics of Parkinson's disease: Progress and therapeutic implications</title><author xml:id="author-1"><persName><forename type="first">Andrew B.</forename><surname>Singleton</surname></persName><roleName type="degree">PhD</roleName><email>singleta@mail.nih.gov</email><affiliation>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Maryland, Bethesda, USA</affiliation></author><author xml:id="author-2"><persName><forename type="first">Matthew J.</forename><surname>Farrer</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, Canada</affiliation></author><author xml:id="author-3"><persName><forename type="first">Vincenzo</forename><surname>Bonifati</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Clinical Genetics, Rotterdam, Erasmus MC, The Netherlands</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov Disord</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-01"></date><biblScope unit="volume">28</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="14">14</biblScope><biblScope unit="page" to="23">23</biblScope></imprint></monogr><idno type="istex">1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC</idno><idno type="DOI">10.1002/mds.25249</idno><idno type="ArticleID">MDS25249</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2013-01-17</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease‐causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second‐generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha‐synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology‐based therapeutic approaches in this disease. © 2013 Movement Disorder Society</p></abstract><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>genetics</term></item><item><term>Parkinson‐s disease</term></item><item><term>therapeutics</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Review</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2012-04-25">Received</change><change when="2012-09-20">Registration</change><change when="2013-01-17">Created</change><change when="2013-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api-v5.istex.fr/document/1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC/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" xml:id="mds25249"><header><publicationMeta level="product"><doi origin="wiley" registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov Disord</title></titleGroup></publicationMeta><publicationMeta level="part" position="10"><doi>10.1002/mds.v28.1</doi><titleGroup><title type="specialIssueTitle">The Vatican Conference on Neuroprotection in Parkinson's Disease</title></titleGroup><copyright ownership="publisher">Copyright © 2013 Movement Disorder Society</copyright><numberingGroup><numbering type="journalVolume" number="28">28</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2013-01">January 2013</coverDate></publicationMeta><publicationMeta level="unit" position="40" type="reviewArticle" status="forIssue"><doi>10.1002/mds.25249</doi><idGroup><id type="unit" value="MDS25249"></id></idGroup><countGroup><count type="pageTotal" number="10"></count></countGroup><titleGroup><title type="articleCategory">Review</title><title type="tocHeading1">Reviews</title></titleGroup><copyright ownership="publisher">Copyright © 2013 Movement Disorders Society</copyright><eventGroup><event type="manuscriptReceived" date="2012-04-25"></event><event type="manuscriptRevised" date="2012-08-22"></event><event type="manuscriptAccepted" date="2012-09-20"></event><event type="xmlCreated" agent="Cenveo Publisher Services" date="2013-01-17"></event><event type="publishedOnlineEarlyUnpaginated" date="2013-02-06"></event><event type="firstOnline" date="2013-02-06"></event><event type="publishedOnlineFinalForm" date="2013-02-06"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.6.4 mode:FullText" date="2015-10-03"></event></eventGroup><numberingGroup><numbering type="pageFirst">14</numbering><numbering type="pageLast">23</numbering></numberingGroup><correspondenceTo><b>Correspondence to:</b> Dr. Andrew B. Singleton, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A1014, 35 Convent Drive, Bethesda, Maryland 20892, USA; <email>singleta@mail.nih.gov</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS25249.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">The genetics of <fc>P</fc>arkinson's disease: Progress and therapeutic implications</title><title type="short">The Genetics of PD</title></titleGroup><creators><creator affiliationRef="#mds25249-aff-0001" corresponding="yes" creatorRole="author" xml:id="mds25249-cr-0001"><personName><givenNames>Andrew B.</givenNames><familyName>Singleton</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#mds25249-aff-0002" creatorRole="author" xml:id="mds25249-cr-0002"><personName><givenNames>Matthew J.</givenNames><familyName>Farrer</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#mds25249-aff-0003" creatorRole="author" xml:id="mds25249-cr-0003"><personName><givenNames>Vincenzo</givenNames><familyName>Bonifati</familyName><degrees>MD, PhD</degrees></personName></creator></creators><affiliationGroup><affiliation type="organization" xml:id="mds25249-aff-0001" countryCode="US"><orgDiv>Laboratory of Neurogenetics</orgDiv><orgDiv>National Institute on Aging</orgDiv><orgName>National Institutes of Health</orgName><address><city>Bethesda</city><countryPart>Maryland</countryPart><country>USA</country></address></affiliation><affiliation type="organization" xml:id="mds25249-aff-0002" countryCode="CA"><orgDiv>Department of Medical Genetics</orgDiv><orgName>University of British Columbia</orgName><address><city>Vancouver</city><country>Canada</country></address></affiliation><affiliation type="organization" xml:id="mds25249-aff-0003" countryCode="NL"><orgName>Department of Clinical Genetics</orgName><address><city>Erasmus MC</city><countryPart>Rotterdam</countryPart><country>The Netherlands</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="mds25249-kwd-0001">genetics</keyword><keyword xml:id="mds25249-kwd-0002"><fc>P</fc>arkinson‐s disease</keyword><keyword xml:id="mds25249-kwd-0003">therapeutics</keyword></keywordGroup><abstractGroup><abstract type="main"><p>The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (<fc>PD</fc>). Notably, whereas most mutations, such as those in <i><fc>SNCA</fc>, <fc>PINK1</fc></i>, <i><fc>PARK2</fc></i>, <i><fc>PARK7</fc></i>, <i><fc>PLA2G6</fc></i>, <i><fc>FBXO7</fc></i>, and <i><fc>ATP13A2</fc></i>, are a rare cause of disease, one particular mutation in <i><fc>LRRK2</fc></i> has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease‐causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second‐generation sequencing methods have facilitated the identification of new mutations in <fc>PD</fc>. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha‐synuclein and inhibition of <fc>Lrrk2</fc> kinase activity. We believe this has been an exciting, productive time for <fc>PD</fc> genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology‐based therapeutic approaches in this disease. © 2013 <i>Movement</i> Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="mds25249-note-0001"><p><b>Funding agencies</b>: This work was supported, in part, by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (project no.: Z01 AG000949‐06). This study was supported by grants from the “Internationaal Parkinson Fonds,” The Netherlands, and the Netherlands Organization for Scientific Research (NWO, VIDI grant; to V.B.).</p></note><note xml:id="mds25249-note-0002"><p><b>Relevant conflicts of interest/financial disclosures</b>: Nothing to report.</p></note><note xml:id="mds25249-note-0003"><p>Full financial disclosures and author roles may be found in the online version of this article.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The genetics of Parkinson's disease: Progress and therapeutic implications</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>The Genetics of PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>The genetics of Parkinson's disease: Progress and therapeutic implications</title></titleInfo><name type="personal"><namePart type="given">Andrew B.</namePart><namePart type="family">Singleton</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Maryland, Bethesda, USA</affiliation><affiliation>E-mail: singleta@mail.nih.gov</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Matthew J.</namePart><namePart type="family">Farrer</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vincenzo</namePart><namePart type="family">Bonifati</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Clinical Genetics, Rotterdam, Erasmus MC, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="reviewArticle"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2013-01</dateIssued><dateCreated encoding="w3cdtf">2013-01-17</dateCreated><dateCaptured encoding="w3cdtf">2012-04-25</dateCaptured><dateValid encoding="w3cdtf">2012-09-20</dateValid><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease‐causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second‐generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha‐synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology‐based therapeutic approaches in this disease. © 2013 Movement Disorder Society</abstract><subject><genre>keywords</genre><topic>genetics</topic><topic>Parkinson‐s disease</topic><topic>therapeutics</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov Disord</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Review</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2013</date><detail type="title"><title>The Vatican Conference on Neuroprotection in Parkinson's Disease</title></detail><detail type="volume"><caption>vol.</caption><number>28</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>14</start><end>23</end><total>10</total></extent></part></relatedItem><identifier type="istex">1897BB23048D40AB2FDCC914B29DCA3B9F6AD5AC</identifier><identifier type="DOI">10.1002/mds.25249</identifier><identifier type="ArticleID">MDS25249</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2013 Movement Disorder SocietyCopyright © 2013 Movement Disorders Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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