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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage</title><author><name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Rousseaux, Maxime W C" sort="Rousseaux, Maxime W C" uniqKey="Rousseaux M" first="Maxime W. C." last="Rousseaux">Maxime W. C. Rousseaux</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Phillips, Maryam" sort="Phillips, Maryam" uniqKey="Phillips M" first="Maryam" last="Phillips">Maryam Phillips</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name><affiliation><nlm:aff id="aff2">The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1;</nlm:aff></affiliation></author><author><name sortKey="Bland, Ross J" sort="Bland, Ross J" uniqKey="Bland R" first="Ross J." last="Bland">Ross J. Bland</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Neurologix, Inc., 460 West 12th Avenue, 911 BRT, Columbus, OH 43210</nlm:aff></affiliation></author><author><name sortKey="Callaghan, Steve" sort="Callaghan, Steve" uniqKey="Callaghan S" first="Steve" last="Callaghan">Steve Callaghan</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="During, Matthew J" sort="During, Matthew J" uniqKey="During M" first="Matthew J." last="During">Matthew J. During</name><affiliation><nlm:aff id="aff4">College of Medicine and Public Health, Molecular Virology, Immunology, and Medical Genetics, 455 East Wiseman Hall, 410 West 12th Avenue, Columbus, OH 43210</nlm:aff></affiliation></author><author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><affiliation><nlm:aff id="aff2">The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1;</nlm:aff></affiliation></author><author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18003894</idno><idno type="pmc">2141848</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141848</idno><idno type="RBID">PMC:2141848</idno><idno type="doi">10.1073/pnas.0709379104</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000660</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000660</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage</title><author><name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Rousseaux, Maxime W C" sort="Rousseaux, Maxime W C" uniqKey="Rousseaux M" first="Maxime W. C." last="Rousseaux">Maxime W. C. Rousseaux</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Phillips, Maryam" sort="Phillips, Maryam" uniqKey="Phillips M" first="Maryam" last="Phillips">Maryam Phillips</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name><affiliation><nlm:aff id="aff2">The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1;</nlm:aff></affiliation></author><author><name sortKey="Bland, Ross J" sort="Bland, Ross J" uniqKey="Bland R" first="Ross J." last="Bland">Ross J. Bland</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Neurologix, Inc., 460 West 12th Avenue, 911 BRT, Columbus, OH 43210</nlm:aff></affiliation></author><author><name sortKey="Callaghan, Steve" sort="Callaghan, Steve" uniqKey="Callaghan S" first="Steve" last="Callaghan">Steve Callaghan</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author><author><name sortKey="During, Matthew J" sort="During, Matthew J" uniqKey="During M" first="Matthew J." last="During">Matthew J. During</name><affiliation><nlm:aff id="aff4">College of Medicine and Public Health, Molecular Virology, Immunology, and Medical Genetics, 455 East Wiseman Hall, 410 West 12th Avenue, Columbus, OH 43210</nlm:aff></affiliation></author><author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><affiliation><nlm:aff id="aff2">The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1;</nlm:aff></affiliation></author><author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><affiliation><nlm:aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Recent evidence has indicated that common mechanisms play roles among multiple neurological diseases. However, the specifics of these pathways are not completely understood. Stroke is caused by the interruption of blood flow to the brain, and cumulative evidence supports the critical role of oxidative stress in the ensuing neuronal death process. DJ-1 (<italic>PARK7</italic>) has been identified as the gene linked to early-onset familial Parkinson's disease. Currently, our work also shows that DJ-1 is central to death in both <italic>in Vitro</italic> and <italic>in Vivo</italic> models of stroke. Loss of DJ-1 increases the sensitivity to excitotoxicity and ischemia, whereas expression of DJ-1 can reverse this sensitivity and indeed provide further protection. Importantly, DJ-1 expression decreases markers of oxidative stress after stroke insult <italic>in Vivo</italic>, suggesting that DJ-1 protects through alleviation of oxidative stress. Consistent with this finding, we demonstrate the essential role of the oxidation-sensitive cysteine-106 residue in the neuroprotective activity of DJ-1 after stroke. Our work provides an important example of how a gene seemingly specific for one disease, in this case Parkinson's disease, also appears to be central in other neuropathological conditions such as stroke. It also highlights the important commonalities among differing neuropathologies.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18003894</article-id><article-id pub-id-type="pmc">2141848</article-id><article-id pub-id-type="publisher-id">8371</article-id><article-id pub-id-type="doi">10.1073/pnas.0709379104</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Neuroscience</subject></subj-group></subj-group></article-categories><title-group><article-title>The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Aleyasin</surname><given-names>Hossein</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Rousseaux</surname><given-names>Maxime W. C.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Phillips</surname><given-names>Maryam</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Raymond H.</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bland</surname><given-names>Ross J.</given-names></name><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Callaghan</surname><given-names>Steve</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Slack</surname><given-names>Ruth S.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>During</surname><given-names>Matthew J.</given-names></name><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mak</surname><given-names>Tak W.</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref><xref ref-type="corresp" rid="cor1"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>David S.</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="corresp" rid="cor1"><sup>¶</sup></xref></contrib><aff id="aff1">*Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;</aff><aff id="aff2"><sup>†</sup>The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1;</aff><aff id="aff3"><sup>‡</sup>Neurologix, Inc., 460 West 12th Avenue, 911 BRT, Columbus, OH 43210; and</aff><aff id="aff4"><sup>§</sup>College of Medicine and Public Health, Molecular Virology, Immunology, and Medical Genetics, 455 East Wiseman Hall, 410 West 12th Avenue, Columbus, OH 43210</aff></contrib-group><author-notes><corresp id="cor1"><sup>¶</sup>To whom correspondence may be addressed. E-mail: <email>tmak@uhnres.utoronto.ca</email> or <email>dpark@uottawa.ca</email></corresp><fn fn-type="con"><p>Contributed by Tak W. Mak, October 4, 2007</p></fn><fn fn-type="con"><p>Author contributions: T.W.M. and D.S.P. contributed equally to this work; H.A., M.W.C.R., M.P., T.W.M., and D.S.P. designed research; H.A., M.W.C.R., M.P., and S.C. performed research; R.H.K., R.J.B., S.C., R.S.S., M.J.D., T.W.M., and D.S.P. contributed new reagents/analytic tools; H.A., M.W.C.R., M.P., and D.S.P. analyzed data; and H.A., M.W.C.R., and D.S.P. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>20</day><month>11</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>14</day><month>11</month><year>2007</year></pub-date><volume>104</volume><issue>47</issue><fpage>18748</fpage><lpage>18753</lpage><history><date date-type="received"><day>5</day><month>9</month><year>2007</year></date></history><copyright-statement>© 2007 by The National Academy of Sciences of the USA</copyright-statement><copyright-year>2007</copyright-year><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq04707018748.pdf"></self-uri><abstract><p>Recent evidence has indicated that common mechanisms play roles among multiple neurological diseases. However, the specifics of these pathways are not completely understood. Stroke is caused by the interruption of blood flow to the brain, and cumulative evidence supports the critical role of oxidative stress in the ensuing neuronal death process. DJ-1 (<italic>PARK7</italic>) has been identified as the gene linked to early-onset familial Parkinson's disease. Currently, our work also shows that DJ-1 is central to death in both <italic>in Vitro</italic> and <italic>in Vivo</italic> models of stroke. Loss of DJ-1 increases the sensitivity to excitotoxicity and ischemia, whereas expression of DJ-1 can reverse this sensitivity and indeed provide further protection. Importantly, DJ-1 expression decreases markers of oxidative stress after stroke insult <italic>in Vivo</italic>, suggesting that DJ-1 protects through alleviation of oxidative stress. Consistent with this finding, we demonstrate the essential role of the oxidation-sensitive cysteine-106 residue in the neuroprotective activity of DJ-1 after stroke. Our work provides an important example of how a gene seemingly specific for one disease, in this case Parkinson's disease, also appears to be central in other neuropathological conditions such as stroke. It also highlights the important commonalities among differing neuropathologies.</p></abstract><kwd-group><kwd>neurodegeneration</kwd><kwd>oxidative stress</kwd><kwd>ischemia</kwd><kwd>neuroprotection</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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