Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">CNS expression of glucocerebrosidase corrects α-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy</title><author><name sortKey="Sardi, S Pablo" sort="Sardi, S Pablo" uniqKey="Sardi S" first="S. Pablo" last="Sardi">S. Pablo Sardi</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Clarke, Jennifer" sort="Clarke, Jennifer" uniqKey="Clarke J" first="Jennifer" last="Clarke">Jennifer Clarke</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Kinnecom, Cathrine" sort="Kinnecom, Cathrine" uniqKey="Kinnecom C" first="Cathrine" last="Kinnecom">Cathrine Kinnecom</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Tamsett, Thomas J" sort="Tamsett, Thomas J" uniqKey="Tamsett T" first="Thomas J." last="Tamsett">Thomas J. Tamsett</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Li, Lingyun" sort="Li, Lingyun" uniqKey="Li L" first="Lingyun" last="Li">Lingyun Li</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Stanek, Lisa M" sort="Stanek, Lisa M" uniqKey="Stanek L" first="Lisa M." last="Stanek">Lisa M. Stanek</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Passini, Marco A" sort="Passini, Marco A" uniqKey="Passini M" first="Marco A." last="Passini">Marco A. Passini</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Grabowski, Gregory A" sort="Grabowski, Gregory A" uniqKey="Grabowski G" first="Gregory A." last="Grabowski">Gregory A. Grabowski</name><affiliation><nlm:aff id="aff2"><institution>Cincinnati Children's Hospital Medical Center</institution>, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Ottawa Hospital Research Institute,<institution>University of Ottawa</institution>, Ottawa, ON,<country>Canada</country> K1H 8M5</nlm:aff></affiliation></author><author><name sortKey="Sidman, Richard L" sort="Sidman, Richard L" uniqKey="Sidman R" first="Richard L." last="Sidman">Richard L. Sidman</name><affiliation><nlm:aff id="aff4">Department of Neurology, Beth Israel Deaconess Medical Center,<institution>Harvard Medical School</institution>, Boston, MA 02215</nlm:aff></affiliation></author><author><name sortKey="Cheng, Seng H" sort="Cheng, Seng H" uniqKey="Cheng S" first="Seng H." last="Cheng">Seng H. Cheng</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Shihabuddin, Lamya S" sort="Shihabuddin, Lamya S" uniqKey="Shihabuddin L" first="Lamya S." last="Shihabuddin">Lamya S. Shihabuddin</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21730160</idno><idno type="pmc">3141921</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141921</idno><idno type="RBID">PMC:3141921</idno><idno type="doi">10.1073/pnas.1108197108</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000657</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000657</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">CNS expression of glucocerebrosidase corrects α-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy</title><author><name sortKey="Sardi, S Pablo" sort="Sardi, S Pablo" uniqKey="Sardi S" first="S. Pablo" last="Sardi">S. Pablo Sardi</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Clarke, Jennifer" sort="Clarke, Jennifer" uniqKey="Clarke J" first="Jennifer" last="Clarke">Jennifer Clarke</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Kinnecom, Cathrine" sort="Kinnecom, Cathrine" uniqKey="Kinnecom C" first="Cathrine" last="Kinnecom">Cathrine Kinnecom</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Tamsett, Thomas J" sort="Tamsett, Thomas J" uniqKey="Tamsett T" first="Thomas J." last="Tamsett">Thomas J. Tamsett</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Li, Lingyun" sort="Li, Lingyun" uniqKey="Li L" first="Lingyun" last="Li">Lingyun Li</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Stanek, Lisa M" sort="Stanek, Lisa M" uniqKey="Stanek L" first="Lisa M." last="Stanek">Lisa M. Stanek</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Passini, Marco A" sort="Passini, Marco A" uniqKey="Passini M" first="Marco A." last="Passini">Marco A. Passini</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Grabowski, Gregory A" sort="Grabowski, Gregory A" uniqKey="Grabowski G" first="Gregory A." last="Grabowski">Gregory A. Grabowski</name><affiliation><nlm:aff id="aff2"><institution>Cincinnati Children's Hospital Medical Center</institution>, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Ottawa Hospital Research Institute,<institution>University of Ottawa</institution>, Ottawa, ON,<country>Canada</country> K1H 8M5</nlm:aff></affiliation></author><author><name sortKey="Sidman, Richard L" sort="Sidman, Richard L" uniqKey="Sidman R" first="Richard L." last="Sidman">Richard L. Sidman</name><affiliation><nlm:aff id="aff4">Department of Neurology, Beth Israel Deaconess Medical Center,<institution>Harvard Medical School</institution>, Boston, MA 02215</nlm:aff></affiliation></author><author><name sortKey="Cheng, Seng H" sort="Cheng, Seng H" uniqKey="Cheng S" first="Seng H." last="Cheng">Seng H. Cheng</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</nlm:aff></affiliation></author><author><name sortKey="Shihabuddin, Lamya S" sort="Shihabuddin, Lamya S" uniqKey="Shihabuddin L" first="Lamya S." last="Shihabuddin">Lamya S. Shihabuddin</name><affiliation><nlm:aff id="aff1"><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</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="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model of Gaucher disease (<italic>Gba1<sup>D409V/D409V</sup></italic>) exhibits characteristics of synucleinopathies, including progressive accumulation of proteinase K-resistant α-synuclein/ubiquitin aggregates in hippocampal neurons and a coincident memory deficit. Analysis of homozygous (<italic>Gba1<sup>D409V/D409V</sup></italic>) and heterozygous (<italic>Gba1<sup>D409V/+</sup></italic> and <italic>Gba1<sup>+/−</sup></italic>) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme. Importantly, adeno-associated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of <italic>Gba1<sup>D409V/D409V</sup></italic> mice ameliorated both the histopathological and memory aberrations. The data support the contention that mutations in <italic>GBA1</italic> can cause Parkinson disease-like α-synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeutic strategy for <italic>GBA1</italic>-associated synucleinopathies.</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-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><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">21730160</article-id><article-id pub-id-type="pmc">3141921</article-id><article-id pub-id-type="publisher-id">201108197</article-id><article-id pub-id-type="doi">10.1073/pnas.1108197108</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>CNS expression of glucocerebrosidase corrects α-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sardi</surname><given-names>S. Pablo</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Clarke</surname><given-names>Jennifer</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kinnecom</surname><given-names>Cathrine</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tamsett</surname><given-names>Thomas J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Li</surname><given-names>Lingyun</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stanek</surname><given-names>Lisa M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Passini</surname><given-names>Marco A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Grabowski</surname><given-names>Gregory A.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schlossmacher</surname><given-names>Michael G.</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sidman</surname><given-names>Richard L.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Seng H.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shihabuddin</surname><given-names>Lamya S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><aff id="aff1"><sup>a</sup><institution>Genzyme Corporation</institution>, Framingham, MA 01701;</aff><aff id="aff2"><sup>b</sup><institution>Cincinnati Children's Hospital Medical Center</institution>, Cincinnati, OH 45229;</aff><aff id="aff3"><sup>c</sup>Ottawa Hospital Research Institute,<institution>University of Ottawa</institution>, Ottawa, ON,<country>Canada</country> K1H 8M5; and</aff><aff id="aff4"><sup>d</sup>Department of Neurology, Beth Israel Deaconess Medical Center,<institution>Harvard Medical School</institution>, Boston, MA 02215</aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence may be addressed. E-mail: <email>richard_sidman@hms.harvard.edu</email> or <email>pablo.sardi@genzyme.com</email>.</corresp><fn fn-type="edited-by"><p>Contributed by Richard L. Sidman, May 25, 2011 (sent for review March 3, 2011)</p></fn><fn fn-type="con"><p>Author contributions: S.P.S. and L.S.S. designed research; S.P.S., J.C., C.K., T.J.T., L.L., and L.M.S. performed research; G.A.G. contributed new reagents/analytic tools; S.P.S., J.C., L.L., M.A.P., M.G.S., R.L.S., and L.S.S. analyzed data; and S.P.S., R.L.S., S.H.C., and L.S.S. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>19</day><month>7</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>5</day><month>7</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>5</day><month>7</month><year>2011</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>108</volume><issue>29</issue><fpage>12101</fpage><lpage>12106</lpage><permissions><license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201108197.pdf"></self-uri><abstract><p>Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model of Gaucher disease (<italic>Gba1<sup>D409V/D409V</sup></italic>) exhibits characteristics of synucleinopathies, including progressive accumulation of proteinase K-resistant α-synuclein/ubiquitin aggregates in hippocampal neurons and a coincident memory deficit. Analysis of homozygous (<italic>Gba1<sup>D409V/D409V</sup></italic>) and heterozygous (<italic>Gba1<sup>D409V/+</sup></italic> and <italic>Gba1<sup>+/−</sup></italic>) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme. Importantly, adeno-associated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of <italic>Gba1<sup>D409V/D409V</sup></italic> mice ameliorated both the histopathological and memory aberrations. The data support the contention that mutations in <italic>GBA1</italic> can cause Parkinson disease-like α-synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeutic strategy for <italic>GBA1</italic>-associated synucleinopathies.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 0006570 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 0006570 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.29. |  |