L-dopa increases α-synuclein DNA methylation in Parkinson's disease patients in vivo and in vitro.
Identifieur interne : 000198 ( PubMed/Checkpoint ); précédent : 000197; suivant : 000199L-dopa increases α-synuclein DNA methylation in Parkinson's disease patients in vivo and in vitro.
Auteurs : Ina Schmitt [Allemagne] ; Oliver Kaut [Allemagne] ; Hassan Khazneh [Allemagne] ; Laura Deboni [Allemagne] ; Ashar Ahmad [Allemagne] ; Daniela Berg [Allemagne] ; Christine Klein [Allemagne] ; Holger Fröhlich [Allemagne] ; Ullrich Wüllner [Allemagne]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2015.
Abstract
Increasing gene dosages of α-synuclein induce familial Parkinson's disease (PD); thus, the hypothesis has been put forward that regulation of gene expression, in particular altered α-synuclein gene methylation, might be associated with sporadic PD and could be used as a biological marker.
DOI: 10.1002/mds.26319
PubMed: 26173746
Affiliations:
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last="Schmitt">Ina Schmitt</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, UKB, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, UKB, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Kaut, Oliver" sort="Kaut, Oliver" uniqKey="Kaut O" first="Oliver" last="Kaut">Oliver Kaut</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, UKB, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, UKB, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Khazneh, Hassan" sort="Khazneh, Hassan" uniqKey="Khazneh H" first="Hassan" last="Khazneh">Hassan Khazneh</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, UKB, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, UKB, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Deboni, Laura" sort="Deboni, Laura" uniqKey="Deboni L" first="Laura" last="Deboni">Laura Deboni</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, UKB, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, UKB, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Ahmad, Ashar" sort="Ahmad, Ashar" uniqKey="Ahmad A" first="Ashar" last="Ahmad">Ashar Ahmad</name><affiliation wicri:level="1"><nlm:affiliation>Bonn-Aachen International Center for IT, University of Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bonn-Aachen International Center for IT, University of Bonn</wicri:regionArea><wicri:noRegion>University of Bonn</wicri:noRegion><wicri:noRegion>University of Bonn</wicri:noRegion><wicri:noRegion>University of Bonn</wicri:noRegion></affiliation></author><author><name sortKey="Berg, Daniela" sort="Berg, Daniela" uniqKey="Berg D" first="Daniela" last="Berg">Daniela Berg</name><affiliation wicri:level="3"><nlm:affiliation>German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Center for Neurodegenerative Diseases (DZNE), Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Neurogenetics, University of Lübeck, Lübeck</wicri:regionArea><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Frohlich, Holger" sort="Frohlich, Holger" uniqKey="Frohlich H" first="Holger" last="Fröhlich">Holger Fröhlich</name><affiliation wicri:level="1"><nlm:affiliation>Bonn-Aachen International Center for IT, University of Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bonn-Aachen International Center for IT, University of Bonn</wicri:regionArea><wicri:noRegion>University of Bonn</wicri:noRegion><wicri:noRegion>University of Bonn</wicri:noRegion><wicri:noRegion>University of Bonn</wicri:noRegion></affiliation></author><author><name sortKey="Wullner, Ullrich" sort="Wullner, Ullrich" uniqKey="Wullner U" first="Ullrich" last="Wüllner">Ullrich Wüllner</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, UKB, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, UKB, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Increasing gene dosages of α-synuclein induce familial Parkinson's disease (PD); thus, the hypothesis has been put forward that regulation of gene expression, in particular altered α-synuclein gene methylation, might be associated with sporadic PD and could be used as a biological marker.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">26173746</PMID><DateCreated><Year>2015</Year><Month>7</Month><Day>15</Day></DateCreated><DateRevised><Year>2015</Year><Month>7</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2015</Year><Month>Jul</Month><Day>14</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>L-dopa increases α-synuclein DNA methylation in Parkinson's disease patients in vivo and in vitro.</ArticleTitle><Pagination><MedlinePgn></MedlinePgn></Pagination><ELocationID EIdType="doi">10.1002/mds.26319</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Increasing gene dosages of α-synuclein induce familial Parkinson's disease (PD); thus, the hypothesis has been put forward that regulation of gene expression, in particular altered α-synuclein gene methylation, might be associated with sporadic PD and could be used as a biological marker.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We performed a thorough analysis of α-synuclein methylation in bisulfite-treated DNA from peripheral blood of 490 sporadic PD patients and 485 healthy controls and in addition analyzed the effect of levodopa (l-dopa) on α-synuclein methylation and expression in cultured mononuclear cells.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">α-Synuclein was hypomethylated in sporadic PD patients, correlated with sex, age, and a polymorphism in the analyzed sequence stretch (rs3756063). α-Synuclein methylation separated healthy individuals from sporadic PD with a specificity of 74% (male) and 78% (female), respectively. α-Synuclein methylation was increased in sporadic PD patients with higher l-dopa dosage, and l-dopa specifically induced methylation of α-synuclein intron 1 in cultured mononuclear cells.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">α-Synuclein methylation levels depended on disease status, sex, age, and the genotype of rs3756063. The pharmacological action of l-dopa was not limited to the dopamine precursor function but included epigenetic off-target effects. The hypomethylation of α-synuclein in sporadic PD patients' blood already observed in previous studies was probably underestimated because of effect of l-dopa, which was not known previously. The analysis of α-synuclein methylation can help to identify nonparkinsonian individuals with reasonable specificity, which offers a valuable tool for researchers and clinicians. © 2015 International Parkinson and Movement Disorder Society.</AbstractText><CopyrightInformation>© 2015 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList><Author><LastName>Schmitt</LastName><ForeName>Ina</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Neurology, UKB, Bonn, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>Kaut</LastName><ForeName>Oliver</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Neurology, UKB, Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>Khazneh</LastName><ForeName>Hassan</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Neurology, UKB, Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>deBoni</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Neurology, UKB, Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>Ahmad</LastName><ForeName>Ashar</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Bonn-Aachen International Center for IT, University of Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>Berg</LastName><ForeName>Daniela</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Tübingen, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>Klein</LastName><ForeName>Christine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>Fröhlich</LastName><ForeName>Holger</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Bonn-Aachen International Center for IT, University of Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author><LastName>Wüllner</LastName><ForeName>Ullrich</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Department of Neurology, UKB, Bonn, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.</Affiliation></AffiliationInfo></Author></AuthorList><Language>ENG</Language><PublicationTypeList><PublicationType UI="">JOURNAL ARTICLE</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>7</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">DNA methylation</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">blood</Keyword><Keyword MajorTopicYN="N">l-dopa</Keyword><Keyword MajorTopicYN="N">α-synuclein</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>1</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>5</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>6</Month><Day>3</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>7</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>7</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>7</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.26319</ArticleId><ArticleId IdType="pubmed">26173746</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li></country><region><li>District de Cologne</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Bonn</li></settlement></list><tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Schmitt, Ina" sort="Schmitt, Ina" uniqKey="Schmitt I" first="Ina" last="Schmitt">Ina Schmitt</name></region><name sortKey="Ahmad, Ashar" sort="Ahmad, Ashar" uniqKey="Ahmad A" first="Ashar" last="Ahmad">Ashar Ahmad</name><name sortKey="Berg, Daniela" sort="Berg, Daniela" uniqKey="Berg D" first="Daniela" last="Berg">Daniela Berg</name><name sortKey="Deboni, Laura" sort="Deboni, Laura" uniqKey="Deboni L" first="Laura" last="Deboni">Laura Deboni</name><name sortKey="Frohlich, Holger" sort="Frohlich, Holger" uniqKey="Frohlich H" first="Holger" last="Fröhlich">Holger Fröhlich</name><name sortKey="Kaut, Oliver" sort="Kaut, Oliver" uniqKey="Kaut O" first="Oliver" last="Kaut">Oliver Kaut</name><name sortKey="Khazneh, Hassan" sort="Khazneh, Hassan" uniqKey="Khazneh H" first="Hassan" last="Khazneh">Hassan Khazneh</name><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><name sortKey="Wullner, Ullrich" sort="Wullner, Ullrich" uniqKey="Wullner U" first="Ullrich" last="Wüllner">Ullrich Wüllner</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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