Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects.
Identifieur interne : 000726 ( PubMed/Corpus ); précédent : 000725; suivant : 000727Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects.
Auteurs : Madison T. Gray ; David G. Munoz ; Douglas A. Gray ; Michael G. Schlossmacher ; John M. WoulfeSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Antigens, CD (metabolism), Antigens, CD34 (metabolism), Antigens, Differentiation, Myelomonocytic (metabolism), Gastric Mucosa (metabolism), Gastrointestinal Tract (metabolism), Humans, Macrophages (metabolism), Middle Aged, Nerve Fibers (metabolism), Synaptophysin (metabolism), Ubiquitin Thiolesterase (metabolism), Vasoactive Intestinal Peptide (metabolism), alpha-Synuclein (analysis), alpha-Synuclein (metabolism).
- MESH :
- chemical , analysis : alpha-Synuclein.
- chemical , metabolism : Antigens, CD, Antigens, CD34, Antigens, Differentiation, Myelomonocytic, Synaptophysin, Ubiquitin Thiolesterase, Vasoactive Intestinal Peptide, alpha-Synuclein.
- metabolism : Gastric Mucosa, Gastrointestinal Tract, Macrophages, Nerve Fibers.
- Adult, Aged, Aged, 80 and over, Humans, Middle Aged.
Abstract
Parkinson's disease is characterized by the pathological aggregation of Alpha-synuclein. The dual-hit hypothesis proposed by Braak implicates the enteric nervous system as an initial site of α-synuclein aggregation with subsequent spread to the central nervous system. Regional variations in the spatial pattern or levels of α-synuclein along the enteric nervous system could have implications for identifying sites of onset of this pathogenic cascade. We performed immunohistochemical staining for α-synuclein on gastrointestinal tissue from patients with no history of neurological disease using the established LB509 antibody and a new clone, MJFR1, characterized for immunohistochemistry here. We demonstrate that the vermiform appendix is particularly enriched in α-synuclein-containing axonal varicosities, concentrated in its mucosal plexus rather than the classical submucosal and myenteric plexuses. Unexpectedly, intralysosomal accumulations of α-synuclein were detected within mucosal macrophages of the appendix. The abundance and accumulation of α-synuclein in the vermiform appendix implicate it as a candidate anatomical locus for the initiation of enteric α-synuclein aggregation and permits the generation of testable hypotheses for Parkinson's disease pathogenesis.
DOI: 10.1002/mds.25779
PubMed: 24352892
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Gray</name></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G" last="Schlossmacher">Michael G. Schlossmacher</name></author><author><name sortKey="Woulfe, John M" sort="Woulfe, John M" uniqKey="Woulfe J" first="John M" last="Woulfe">John M. Woulfe</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24352892</idno><idno type="pmid">24352892</idno><idno type="doi">10.1002/mds.25779</idno><idno type="wicri:Area/PubMed/Corpus">000726</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000726</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects.</title><author><name sortKey="Gray, Madison T" sort="Gray, Madison T" uniqKey="Gray M" first="Madison T" last="Gray">Madison T. Gray</name><affiliation><nlm:affiliation>Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Munoz, David G" sort="Munoz, David G" uniqKey="Munoz D" first="David G" last="Munoz">David G. Munoz</name></author><author><name sortKey="Gray, Douglas A" sort="Gray, Douglas A" uniqKey="Gray D" first="Douglas A" last="Gray">Douglas A. Gray</name></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G" last="Schlossmacher">Michael G. Schlossmacher</name></author><author><name sortKey="Woulfe, John M" sort="Woulfe, John M" uniqKey="Woulfe J" first="John M" last="Woulfe">John M. Woulfe</name></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="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Antigens, CD (metabolism)</term><term>Antigens, CD34 (metabolism)</term><term>Antigens, Differentiation, Myelomonocytic (metabolism)</term><term>Gastric Mucosa (metabolism)</term><term>Gastrointestinal Tract (metabolism)</term><term>Humans</term><term>Macrophages (metabolism)</term><term>Middle Aged</term><term>Nerve Fibers (metabolism)</term><term>Synaptophysin (metabolism)</term><term>Ubiquitin Thiolesterase (metabolism)</term><term>Vasoactive Intestinal Peptide (metabolism)</term><term>alpha-Synuclein (analysis)</term><term>alpha-Synuclein (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, CD</term><term>Antigens, CD34</term><term>Antigens, Differentiation, Myelomonocytic</term><term>Synaptophysin</term><term>Ubiquitin Thiolesterase</term><term>Vasoactive Intestinal Peptide</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Gastric Mucosa</term><term>Gastrointestinal Tract</term><term>Macrophages</term><term>Nerve Fibers</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Humans</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease is characterized by the pathological aggregation of Alpha-synuclein. The dual-hit hypothesis proposed by Braak implicates the enteric nervous system as an initial site of α-synuclein aggregation with subsequent spread to the central nervous system. Regional variations in the spatial pattern or levels of α-synuclein along the enteric nervous system could have implications for identifying sites of onset of this pathogenic cascade. We performed immunohistochemical staining for α-synuclein on gastrointestinal tissue from patients with no history of neurological disease using the established LB509 antibody and a new clone, MJFR1, characterized for immunohistochemistry here. We demonstrate that the vermiform appendix is particularly enriched in α-synuclein-containing axonal varicosities, concentrated in its mucosal plexus rather than the classical submucosal and myenteric plexuses. Unexpectedly, intralysosomal accumulations of α-synuclein were detected within mucosal macrophages of the appendix. The abundance and accumulation of α-synuclein in the vermiform appendix implicate it as a candidate anatomical locus for the initiation of enteric α-synuclein aggregation and permits the generation of testable hypotheses for Parkinson's disease pathogenesis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24352892</PMID><DateCreated><Year>2014</Year><Month>07</Month><Day>21</Day></DateCreated><DateCompleted><Year>2015</Year><Month>03</Month><Day>30</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>29</Volume><Issue>8</Issue><PubDate><Year>2014</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects.</ArticleTitle><Pagination><MedlinePgn>991-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.25779</ELocationID><Abstract><AbstractText>Parkinson's disease is characterized by the pathological aggregation of Alpha-synuclein. The dual-hit hypothesis proposed by Braak implicates the enteric nervous system as an initial site of α-synuclein aggregation with subsequent spread to the central nervous system. Regional variations in the spatial pattern or levels of α-synuclein along the enteric nervous system could have implications for identifying sites of onset of this pathogenic cascade. We performed immunohistochemical staining for α-synuclein on gastrointestinal tissue from patients with no history of neurological disease using the established LB509 antibody and a new clone, MJFR1, characterized for immunohistochemistry here. We demonstrate that the vermiform appendix is particularly enriched in α-synuclein-containing axonal varicosities, concentrated in its mucosal plexus rather than the classical submucosal and myenteric plexuses. Unexpectedly, intralysosomal accumulations of α-synuclein were detected within mucosal macrophages of the appendix. The abundance and accumulation of α-synuclein in the vermiform appendix implicate it as a candidate anatomical locus for the initiation of enteric α-synuclein aggregation and permits the generation of testable hypotheses for Parkinson's disease pathogenesis.</AbstractText><CopyrightInformation>© 2013 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gray</LastName><ForeName>Madison T</ForeName><Initials>MT</Initials><AffiliationInfo><Affiliation>Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Munoz</LastName><ForeName>David G</ForeName><Initials>DG</Initials></Author><Author ValidYN="Y"><LastName>Gray</LastName><ForeName>Douglas A</ForeName><Initials>DA</Initials></Author><Author ValidYN="Y"><LastName>Schlossmacher</LastName><ForeName>Michael G</ForeName><Initials>MG</Initials></Author><Author ValidYN="Y"><LastName>Woulfe</LastName><ForeName>John M</ForeName><Initials>JM</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>12</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov 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