MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease
Identifieur interne : 001254 ( Main/Corpus ); précédent : 001253; suivant : 001255MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease
Auteurs : Linda R. White ; Mathias Toft ; Sylvia N. Kvam ; Matthew J. Farrer ; Jan O. AaslySource :
- Journal of Neuroscience Research [ 0360-4012 ] ; 2007-05-01.
English descriptors
- KwdEn :
Abstract
The 6055G>A mutation in the leucine‐rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed‐lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen‐activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S‐associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S‐associated PD. Changes in MAPK‐signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of LRRK2‐associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/jnr.21240
Links to Exploration step
ISTEX:99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EFLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title><author><name sortKey="White, Linda R" sort="White, Linda R" uniqKey="White L" first="Linda R." last="White">Linda R. White</name><affiliation><mods:affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</mods:affiliation></affiliation></author><author><name sortKey="Toft, Mathias" sort="Toft, Mathias" uniqKey="Toft M" first="Mathias" last="Toft">Mathias Toft</name><affiliation><mods:affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</mods:affiliation></affiliation></author><author><name sortKey="Kvam, Sylvia N" sort="Kvam, Sylvia N" uniqKey="Kvam S" first="Sylvia N." last="Kvam">Sylvia N. Kvam</name><affiliation><mods:affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</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 Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida</mods:affiliation></affiliation></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name><affiliation><mods:affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1002/jnr.21240</idno><idno type="url">https://api.istex.fr/document/99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001254</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title><author><name sortKey="White, Linda R" sort="White, Linda R" uniqKey="White L" first="Linda R." last="White">Linda R. White</name><affiliation><mods:affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</mods:affiliation></affiliation></author><author><name sortKey="Toft, Mathias" sort="Toft, Mathias" uniqKey="Toft M" first="Mathias" last="Toft">Mathias Toft</name><affiliation><mods:affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</mods:affiliation></affiliation></author><author><name sortKey="Kvam, Sylvia N" sort="Kvam, Sylvia N" uniqKey="Kvam S" first="Sylvia N." last="Kvam">Sylvia N. Kvam</name><affiliation><mods:affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</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 Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida</mods:affiliation></affiliation></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name><affiliation><mods:affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Neuroscience Research</title><title level="j" type="abbrev">J. Neurosci. Res.</title><idno type="ISSN">0360-4012</idno><idno type="eISSN">1097-4547</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-05-01">2007-05-01</date><biblScope unit="volume">85</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1288">1288</biblScope><biblScope unit="page" to="1294">1294</biblScope></imprint><idno type="ISSN">0360-4012</idno></series><idno type="istex">99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF</idno><idno type="DOI">10.1002/jnr.21240</idno><idno type="ArticleID">JNR21240</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0360-4012</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>HSP27</term><term>JNK</term><term>Parkinson, MAPK signalling</term><term>Src</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The 6055G>A mutation in the leucine‐rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed‐lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen‐activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S‐associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S‐associated PD. Changes in MAPK‐signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of LRRK2‐associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Linda R. White</name><affiliations><json:string>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</json:string><json:string>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</json:string></affiliations></json:item><json:item><name>Mathias Toft</name><affiliations><json:string>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</json:string></affiliations></json:item><json:item><name>Sylvia N. Kvam</name><affiliations><json:string>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</json:string></affiliations></json:item><json:item><name>Matthew J. Farrer</name><affiliations><json:string>Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida</json:string></affiliations></json:item><json:item><name>Jan O. Aasly</name><affiliations><json:string>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</json:string><json:string>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson, MAPK signalling</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HSP27</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>JNK</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Src</value></json:item></subject><articleId><json:string>JNR21240</json:string></articleId><language><json:string>eng</json:string></language><abstract>The 6055G>A mutation in the leucine‐rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed‐lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen‐activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S‐associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S‐associated PD. Changes in MAPK‐signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of LRRK2‐associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>6.754</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>1603</abstractCharCount><pdfWordCount>3934</pdfWordCount><pdfCharCount>25235</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>235</abstractWordCount></qualityIndicators><title>MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title><genre><json:string>article</json:string></genre><host><volume>85</volume><publisherId><json:string>JNR</json:string></publisherId><pages><total>7</total><last>1294</last><first>1288</first></pages><issn><json:string>0360-4012</json:string></issn><issue>6</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1097-4547</json:string></eissn><title>Journal of Neuroscience Research</title><doi><json:string>10.1002/(ISSN)1097-4547</json:string></doi></host><publicationDate>2007</publicationDate><copyrightDate>2007</copyrightDate><doi><json:string>10.1002/jnr.21240</json:string></doi><id>99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2007</date></publicationStmt><notesStmt><note>Research Council of Norway - No. 153487/V50;</note><note>Advocate Rolf Sandberg and Ellen Marie Reberg's Legacy for Parkinson's Disease Research</note><note>Norwegian Parkinson Foundation</note><note>Odd Fellow Medical Research Fund</note><note>Parkinson's Disease Foundation</note><note>National Institute of Aging - No. AG022579;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title><author><persName><forename type="first">Linda R.</forename><surname>White</surname></persName><note type="correspondence"><p>Correspondence: Department of Neurology, University Hospital of Trondheim, Edvard Griegs gt. 8, N‐7006 Trondheim, Norway</p></note><affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</affiliation><affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</affiliation></author><author><persName><forename type="first">Mathias</forename><surname>Toft</surname></persName><affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</affiliation></author><author><persName><forename type="first">Sylvia N.</forename><surname>Kvam</surname></persName><affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</affiliation></author><author><persName><forename type="first">Matthew J.</forename><surname>Farrer</surname></persName><affiliation>Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida</affiliation></author><author><persName><forename type="first">Jan O.</forename><surname>Aasly</surname></persName><affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</affiliation><affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</affiliation></author></analytic><monogr><title level="j">Journal of Neuroscience Research</title><title level="j" type="abbrev">J. Neurosci. Res.</title><idno type="pISSN">0360-4012</idno><idno type="eISSN">1097-4547</idno><idno type="DOI">10.1002/(ISSN)1097-4547</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-05-01"></date><biblScope unit="volume">85</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1288">1288</biblScope><biblScope unit="page" to="1294">1294</biblScope></imprint></monogr><idno type="istex">99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF</idno><idno type="DOI">10.1002/jnr.21240</idno><idno type="ArticleID">JNR21240</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The 6055G>A mutation in the leucine‐rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed‐lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen‐activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S‐associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S‐associated PD. Changes in MAPK‐signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of LRRK2‐associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson, MAPK signalling</term></item><item><term>HSP27</term></item><item><term>JNK</term></item><item><term>Src</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-08-31">Received</change><change when="2006-12-15">Registration</change><change when="2007-05-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF/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>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1097-4547</doi><issn type="print">0360-4012</issn><issn type="electronic">1097-4547</issn><idGroup><id type="product" value="JNR"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="JOURNAL OF NEUROSCIENCE RESEARCH">Journal of Neuroscience Research</title><title type="short">J. Neurosci. Res.</title></titleGroup></publicationMeta><publicationMeta level="part" position="60"><doi origin="wiley" registered="yes">10.1002/jnr.v85:6</doi><numberingGroup><numbering type="journalVolume" number="85">85</numbering><numbering type="journalIssue">6</numbering></numberingGroup><coverDate startDate="2007-05-01">1 May 2007</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="140" status="forIssue"><doi origin="wiley" registered="yes">10.1002/jnr.21240</doi><idGroup><id type="unit" value="JNR21240"></id></idGroup><countGroup><count type="pageTotal" number="7"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="publisher">Copyright © 2007 Wiley‐Liss, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2006-08-31"></event><event type="manuscriptRevised" date="2006-12-14"></event><event type="manuscriptAccepted" date="2006-12-15"></event><event type="publishedOnlineEarlyUnpaginated" date="2007-03-26"></event><event type="firstOnline" date="2007-03-26"></event><event type="publishedOnlineFinalForm" date="2007-04-13"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.6 mode:FullText source:FullText result:FullText" date="2010-04-20"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-31"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-30"></event></eventGroup><numberingGroup><numbering type="pageFirst">1288</numbering><numbering type="pageLast">1294</numbering></numberingGroup><correspondenceTo>Department of Neurology, University Hospital of Trondheim, Edvard Griegs gt. 8, N‐7006 Trondheim, Norway</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JNR.JNR21240.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="5"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="25"></count><count type="wordTotal" number="4406"></count></countGroup><titleGroup><title type="main" xml:lang="en">MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title><title type="short" xml:lang="en">MAPK Signalling and Parkinson's Disease</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2" corresponding="yes"><personName><givenNames>Linda R.</givenNames><familyName>White</familyName></personName><contactDetails><email>linda.white@ntnu.no</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Mathias</givenNames><familyName>Toft</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Sylvia N.</givenNames><familyName>Kvam</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Matthew J.</givenNames><familyName>Farrer</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Jan O.</givenNames><familyName>Aasly</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="NO" type="organization"><unparsedAffiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="NO" type="organization"><unparsedAffiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson, MAPK signalling</keyword><keyword xml:id="kwd2">HSP27</keyword><keyword xml:id="kwd3">JNK</keyword><keyword xml:id="kwd4">Src</keyword></keywordGroup><fundingInfo><fundingAgency>Research Council of Norway</fundingAgency><fundingNumber>153487/V50</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Advocate Rolf Sandberg and Ellen Marie Reberg's Legacy for Parkinson's Disease Research</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Norwegian Parkinson Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Odd Fellow Medical Research Fund</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Parkinson's Disease Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Institute of Aging</fundingAgency><fundingNumber>AG022579</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The <i>6055G>A</i> mutation in the <i>leucine‐rich repeat kinase 2</i> (<i>LRRK2</i>) gene results in a G2019S substitution in the mixed‐lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen‐activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S‐associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S‐associated PD. Changes in MAPK‐signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of <i>LRRK2</i>‐associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>MAPK Signalling and Parkinson's Disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Linda R.</namePart><namePart type="family">White</namePart><affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</affiliation><affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</affiliation><description>Correspondence: Department of Neurology, University Hospital of Trondheim, Edvard Griegs gt. 8, N‐7006 Trondheim, Norway</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mathias</namePart><namePart type="family">Toft</namePart><affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sylvia N.</namePart><namePart type="family">Kvam</namePart><affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Matthew J.</namePart><namePart type="family">Farrer</namePart><affiliation>Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan O.</namePart><namePart type="family">Aasly</namePart><affiliation>Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway</affiliation><affiliation>Department of Neurology, University Hospital of Trondheim, Trondheim, Norway</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2007-05-01</dateIssued><dateCaptured encoding="w3cdtf">2006-08-31</dateCaptured><dateValid encoding="w3cdtf">2006-12-15</dateValid><copyrightDate encoding="w3cdtf">2007</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">5</extent><extent unit="tables">2</extent><extent unit="references">25</extent><extent unit="words">4406</extent></physicalDescription><abstract lang="en">The 6055G>A mutation in the leucine‐rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed‐lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen‐activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S‐associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S‐associated PD. Changes in MAPK‐signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of LRRK2‐associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley‐Liss, Inc.</abstract><note type="funding">Research Council of Norway - No. 153487/V50; </note><note type="funding">Advocate Rolf Sandberg and Ellen Marie Reberg's Legacy for Parkinson's Disease Research</note><note type="funding">Norwegian Parkinson Foundation</note><note type="funding">Odd Fellow Medical Research Fund</note><note type="funding">Parkinson's Disease Foundation</note><note type="funding">National Institute of Aging - No. AG022579; </note><subject lang="en"><genre>Keywords</genre><topic>Parkinson, MAPK signalling</topic><topic>HSP27</topic><topic>JNK</topic><topic>Src</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Neuroscience Research</title></titleInfo><titleInfo type="abbreviated"><title>J. Neurosci. Res.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0360-4012</identifier><identifier type="eISSN">1097-4547</identifier><identifier type="DOI">10.1002/(ISSN)1097-4547</identifier><identifier type="PublisherID">JNR</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>85</number></detail><detail type="issue"><caption>no.</caption><number>6</number></detail><extent unit="pages"><start>1288</start><end>1294</end><total>7</total></extent></part></relatedItem><identifier type="istex">99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF</identifier><identifier type="DOI">10.1002/jnr.21240</identifier><identifier type="ArticleID">JNR21240</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2007 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001254 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 001254 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:99BA7B48AF9B6C7AEC7537AB5C00EC3E370F06EF
|texte= MAPK‐pathway activity, Lrrk2 G2019S, and Parkinson's disease
}}
| This area was generated with Dilib version V0.6.23. |  |