No Evidence for Substrate Accumulation in Parkinson Brains With GBA Mutations
Identifieur interne : 000146 ( Main/Exploration ); précédent : 000145; suivant : 000147No Evidence for Substrate Accumulation in Parkinson Brains With GBA Mutations
Auteurs : Matthew E. Gegg [Royaume-Uni] ; Lindsay Sweet [États-Unis] ; Bing H. Wang [États-Unis] ; Lamya S. Shihabuddin [États-Unis] ; Sergio Pablo Sardi [États-Unis] ; Anthony H. V. Schapira [Royaume-Uni]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2015.
Abstract
To establish whether Parkinson’s disease (PD) brains previously described to have decreased glucocerebrosidase activity exhibit accumulation of the lysosomal enzyme’s substrate, glucosylceramide, or other changes in lipid composition.
Lipidomic analyses and cholesterol measurements were performed on the putamen (n = 5-7) and cerebellum (n = 7-14) of controls, Parkinson’s disease brains with heterozygote
Total glucosylceramide levels were unchanged in both PD+GBA and sporadic PD brains when compared with controls. No changes in glucosylsphingosine (deacetylated glucosylceramide), sphingomyelin, gangliosides (GM2, GM3), or total cholesterol were observed in either putamen or cerebellum.
This study did not demonstrate glucocerebrosidase substrate accumulation in PD brains with heterozygote
Url:
DOI: 10.1002/mds.26278
PubMed: 26096906
PubMed Central: 4529481
Affiliations:
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Gegg</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Sweet, Lindsay" sort="Sweet, Lindsay" uniqKey="Sweet L" first="Lindsay" last="Sweet">Lindsay Sweet</name><affiliation wicri:level="2"><nlm:aff id="A2">Genzyme, a Sanofi Company, Framingham, Massachusetts, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genzyme, a Sanofi Company, Framingham, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Wang, Bing H" sort="Wang, Bing H" uniqKey="Wang B" first="Bing H." last="Wang">Bing H. Wang</name><affiliation wicri:level="2"><nlm:aff id="A2">Genzyme, a Sanofi Company, Framingham, Massachusetts, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genzyme, a Sanofi Company, Framingham, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></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 wicri:level="2"><nlm:aff id="A2">Genzyme, a Sanofi Company, Framingham, Massachusetts, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genzyme, a Sanofi Company, Framingham, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Sardi, Sergio Pablo" sort="Sardi, Sergio Pablo" uniqKey="Sardi S" first="Sergio Pablo" last="Sardi">Sergio Pablo Sardi</name><affiliation wicri:level="2"><nlm:aff id="A2">Genzyme, a Sanofi Company, Framingham, Massachusetts, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genzyme, a Sanofi Company, Framingham, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Schapira, Anthony H V" sort="Schapira, Anthony H V" uniqKey="Schapira A" first="Anthony H. V." last="Schapira">Anthony H. V. Schapira</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Clinical Neuroscience, UCL Institute of Neurology, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">To establish whether Parkinson’s disease (PD) brains previously described to have decreased glucocerebrosidase activity exhibit accumulation of the lysosomal enzyme’s substrate, glucosylceramide, or other changes in lipid composition.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Lipidomic analyses and cholesterol measurements were performed on the putamen (n = 5-7) and cerebellum (n = 7-14) of controls, Parkinson’s disease brains with heterozygote <italic>GBA1</italic> mutations (PD+GBA), or sporadic PD.</p></sec><sec id="S3"><title>Results</title><p id="P3">Total glucosylceramide levels were unchanged in both PD+GBA and sporadic PD brains when compared with controls. No changes in glucosylsphingosine (deacetylated glucosylceramide), sphingomyelin, gangliosides (GM2, GM3), or total cholesterol were observed in either putamen or cerebellum.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">This study did not demonstrate glucocerebrosidase substrate accumulation in PD brains with heterozygote <italic>GBA1</italic> mutations in areas of the brain with low α-synuclein pathology.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sidransky, E" uniqKey="Sidransky E">E Sidransky</name></author><author><name sortKey="Nalls, Ma" uniqKey="Nalls M">MA Nalls</name></author><author><name sortKey="Aasly, Jo" uniqKey="Aasly J">JO Aasly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neumann, J" uniqKey="Neumann J">J Neumann</name></author><author><name sortKey="Bras, J" uniqKey="Bras J">J Bras</name></author><author><name sortKey="Deas, E" uniqKey="Deas E">E 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A">AM Cuervo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodriguez Navarro, Ja" uniqKey="Rodriguez Navarro J">JA Rodriguez-Navarro</name></author><author><name sortKey="Kaushik, S" uniqKey="Kaushik S">S Kaushik</name></author><author><name sortKey="Koga, H" uniqKey="Koga H">H Koga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fabelo, N" uniqKey="Fabelo N">N Fabelo</name></author><author><name sortKey="Martin, V" uniqKey="Martin V">V Martín</name></author><author><name sortKey="Santpere, G" uniqKey="Santpere G">G Santpere</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brockmann, K" uniqKey="Brockmann K">K Brockmann</name></author><author><name sortKey="Hilker, R" uniqKey="Hilker R">R Hilker</name></author><author><name sortKey="Pilatus, U" uniqKey="Pilatus U">U Pilatus</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Massachusetts</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Gegg, Matthew E" sort="Gegg, Matthew E" uniqKey="Gegg M" first="Matthew E." last="Gegg">Matthew E. Gegg</name></region><name sortKey="Schapira, Anthony H V" sort="Schapira, Anthony H V" uniqKey="Schapira A" first="Anthony H. V." last="Schapira">Anthony H. V. Schapira</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Sweet, Lindsay" sort="Sweet, Lindsay" uniqKey="Sweet L" first="Lindsay" last="Sweet">Lindsay Sweet</name></region><name sortKey="Sardi, Sergio Pablo" sort="Sardi, Sergio Pablo" uniqKey="Sardi S" first="Sergio Pablo" last="Sardi">Sergio Pablo Sardi</name><name sortKey="Shihabuddin, Lamya S" sort="Shihabuddin, Lamya S" uniqKey="Shihabuddin L" first="Lamya S." last="Shihabuddin">Lamya S. Shihabuddin</name><name sortKey="Wang, Bing H" sort="Wang, Bing H" uniqKey="Wang B" first="Bing H." last="Wang">Bing H. Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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