α-Synuclein oligomers and clinical implications for Parkinson disease
Identifieur interne : 000735 ( Pmc/Checkpoint ); précédent : 000734; suivant : 000736α-Synuclein oligomers and clinical implications for Parkinson disease
Auteurs : Lorraine V. Kalia [Canada] ; Suneil K. Kalia [Canada] ; Pamela J. Mclean [États-Unis] ; Andres M. Lozano [Canada] ; Anthony E. Lang [Canada]Source :
- Annals of neurology [ 0364-5134 ] ; 2012.
Abstract
Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications.
Url:
DOI: 10.1002/ana.23746
PubMed: 23225525
PubMed Central: 3608838
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:3608838Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">α-Synuclein oligomers and clinical implications for Parkinson disease</title>
<author><name sortKey="Kalia, Lorraine V" sort="Kalia, Lorraine V" uniqKey="Kalia L" first="Lorraine V." last="Kalia">Lorraine V. Kalia</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mclean, Pamela J" sort="Mclean, Pamela J" uniqKey="Mclean P" first="Pamela J." last="Mclean">Pamela J. Mclean</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL</wicri:regionArea>
<wicri:noRegion>FL</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23225525</idno>
<idno type="pmc">3608838</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608838</idno>
<idno type="RBID">PMC:3608838</idno>
<idno type="doi">10.1002/ana.23746</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000797</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000797</idno>
<idno type="wicri:Area/Pmc/Curation">000797</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000797</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000735</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000735</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">α-Synuclein oligomers and clinical implications for Parkinson disease</title>
<author><name sortKey="Kalia, Lorraine V" sort="Kalia, Lorraine V" uniqKey="Kalia L" first="Lorraine V." last="Kalia">Lorraine V. Kalia</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mclean, Pamela J" sort="Mclean, Pamela J" uniqKey="Mclean P" first="Pamela J." last="Mclean">Pamela J. Mclean</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL</wicri:regionArea>
<wicri:noRegion>FL</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Annals of neurology</title>
<idno type="ISSN">0364-5134</idno>
<idno type="eISSN">1531-8249</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20<sup>th</sup>
century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications.</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>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">7707449</journal-id>
<journal-id journal-id-type="pubmed-jr-id">656</journal-id>
<journal-id journal-id-type="nlm-ta">Ann Neurol</journal-id>
<journal-id journal-id-type="iso-abbrev">Ann. Neurol.</journal-id>
<journal-title-group><journal-title>Annals of neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0364-5134</issn>
<issn pub-type="epub">1531-8249</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23225525</article-id>
<article-id pub-id-type="pmc">3608838</article-id>
<article-id pub-id-type="doi">10.1002/ana.23746</article-id>
<article-id pub-id-type="manuscript">NIHMS403731</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>α-Synuclein oligomers and clinical implications for Parkinson disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kalia</surname>
<given-names>Lorraine V.</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kalia</surname>
<given-names>Suneil K.</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McLean</surname>
<given-names>Pamela J.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lozano</surname>
<given-names>Andres M.</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lang</surname>
<given-names>Anthony E.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</aff>
<aff id="A2"><label>2</label>
Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada</aff>
<aff id="A3"><label>3</label>
Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</aff>
<aff id="A4"><label>4</label>
Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA</aff>
<author-notes><corresp id="FN1">Corresponding author: Dr. Anthony Lang, Movement Disorders Centre, Toronto Western Hospital, 399 Bathurst Street, McL 7, Toronto, Ontario, M5T 2S8, Canada, Phone: 416-603-6422, Fax: 416-603-5004, <email>lang@uhnres.utoronto.ca</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>20</day>
<month>9</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>07</day>
<month>12</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub"><month>2</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>2</month>
<year>2014</year>
</pub-date>
<volume>73</volume>
<issue>2</issue>
<fpage>155</fpage>
<lpage>169</lpage>
<abstract><p id="P1">Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20<sup>th</sup>
century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications.</p>
</abstract>
<funding-group><award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS063963 || NS</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Canada</li>
<li>États-Unis</li>
</country>
<region><li>Ontario</li>
</region>
<settlement><li>Toronto</li>
</settlement>
<orgName><li>Université de Toronto</li>
</orgName>
</list>
<tree><country name="Canada"><region name="Ontario"><name sortKey="Kalia, Lorraine V" sort="Kalia, Lorraine V" uniqKey="Kalia L" first="Lorraine V." last="Kalia">Lorraine V. Kalia</name>
</region>
<name sortKey="Kalia, Lorraine V" sort="Kalia, Lorraine V" uniqKey="Kalia L" first="Lorraine V." last="Kalia">Lorraine V. Kalia</name>
<name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name>
<name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name>
<name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name>
<name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Mclean, Pamela J" sort="Mclean, Pamela J" uniqKey="Mclean P" first="Pamela J." last="Mclean">Pamela J. Mclean</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000735 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 000735 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Canada |area= ParkinsonCanadaV1 |flux= Pmc |étape= Checkpoint |type= RBID |clé= PMC:3608838 |texte= α-Synuclein oligomers and clinical implications for Parkinson disease }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:23225525" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a ParkinsonCanadaV1
This area was generated with Dilib version V0.6.29. |