Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation
Identifieur interne : 000469 ( PascalFrancis/Corpus ); précédent : 000468; suivant : 000470Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation
Auteurs : JUNCHAO TONG ; Henry Wong ; Mark Guttman ; Lee C. Ang ; Lysia S. Forno ; Mitsunobu Shimadzu ; Ali H. Rajput ; Manfred D. Muenter ; Stephen J. Kish ; Oleh Hornykiewicz ; Yoshiaki FurukawaSource :
- Brain [ 0006-8950 ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
α-synuclein is a major component of Lewy bodies and glial cytoplasmic inclusions, pathological hallmarks of idiopathic Parkinson's disease and multiple system atrophy, and it is assumed to be aetiologically involved in these conditions. However, the quantitative status of brain α-synuclein in different Parkinsonian disorders is still unresolved and it is uncertain whether α-synuclein accumulation is restricted to regions of pathology. We compared membrane-associated, sodium dodecyl sulfate-soluble α-synuclein, both the full-length 17 kDa and high molecular weight species, by western blotting in autopsied brain of patients with Parkinson's disease (brainstem-predominant Lewy body disease: n=9), multiple system atrophy (n=11), progressive supranuclear palsy (n = 16), and of normal controls (n = 13). Brain of a patient with familial Parkinsonism-dementia due to α-synuclein locus triplication (as positive control) showed increased membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels with abundant high molecular weight immunoreactivity. In multiple system atrophy, a massive increase in 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein was observed in highly pathologically affected regions, including putamen (+1760%, range +625-2900%), substantia nigra [+1000% (+356-1850%)], and white matter of internal capsule [+2210% (+430-6830%)] together with numerous high molecular weight species. Levels of 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were only modestly increased in less affected areas (cerebellar cortex, +95%; caudate, +30%; with both also showing numerous high molecular weight species) and were generally normal in cerebral cortices. In both Parkinson's disease and progressive supranuclear palsy, membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels were normal in putamen and frontal cortex whereas a trend was observed for variably increased 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synudein concentrations [+184% (-60% to +618%)] with additional high molecular weight species in Parkinson's disease substantia nigra. No obvious correlation was observed between nigral membrane-associated, sodium dodecyl sulfate-soluble (α-synuclein accumulation and Lewy body density in Parkinson's disease. Two progressive supranuclear palsy cases had membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in substantia nigra similar to multiple system atrophy. Several Parkinson's disease patients had very modest high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in putamen. Levels of 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were generally positively correlated with those of high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein and there was a trend for a positive correlation between striatal dopamine loss and 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein concentrations in multiple system atrophy. Brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulations in Parkinson's disease and multiple system atrophy are regionally specific, suggesting that these sporadic α-synucleinopathies, unlike familial Parkinsonism-dementia, are not associated with a simple global over-expression of the protein. Despite a similar extent of dopamine depletion, the magnitude of brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein changes is disease specific, with multiple system atrophy clearly having the most severe accumulation. Literature discrepancies on α-synuclein status in 'Parkinson's disease' might be explained by inclusion of cases not having classic brainstem-predominant Lewy body disease and by variable α-synuclein accumulation within this diagnostic classification.
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Format Inist (serveur)
| NO : | PASCAL 10-0060219 INIST |
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| ET : | Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation |
| AU : | JUNCHAO TONG; WONG (Henry); GUTTMAN (Mark); ANG (Lee C.); FORNO (Lysia S.); SHIMADZU (Mitsunobu); RAJPUT (Ali H.); MUENTER (Manfred D.); KISH (Stephen J.); HORNYKIEWICZ (Oleh); FURUKAWA (Yoshiaki) |
| AF : | Movement Disorders Research Laboratory, Centre for Addiction and Mental Health/Toronto, Ontario/Canada (1 aut., 2 aut., 11 aut.); Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health/Toronto, Ontario/Canada (1 aut., 3 aut., 9 aut.); Centre for Movement Disorders/Markham, Ontario/Canada (3 aut.); Department of Pathology, University of Western Ontario/London, Ontario/Canada (4 aut.); Department of Pathology, VA Palo Alto Health Care System/Palo Alto, CA/Etats-Unis (5 aut.); Mitsubishi Chemical Medience Corporation/Tokyo/Japon (6 aut.); Division of Neurology, University of Saskatchewan/Saskatoon, Saskatchewan/Canada (7 aut.); Department of Neurology, Mayo Clinic Scottsdale/Scottsdale, AZ/Etats-Unis (8 aut.); Center for Brain Research, University of Vienna/Vienna/Autriche (10 aut.); Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center/Tokyo/Japon (11 aut.); Department of Neurology, Faculty of Medicine, University & Post Graduate University of Juntendo/Tokyo/Japon (11 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Brain; ISSN 0006-8950; Royaume-Uni; Da. 2010; Vol. 133; No. p. 1; Pp. 172-188; Bibl. 2 p.1/2 |
| LA : | Anglais |
| EA : | α-synuclein is a major component of Lewy bodies and glial cytoplasmic inclusions, pathological hallmarks of idiopathic Parkinson's disease and multiple system atrophy, and it is assumed to be aetiologically involved in these conditions. However, the quantitative status of brain α-synuclein in different Parkinsonian disorders is still unresolved and it is uncertain whether α-synuclein accumulation is restricted to regions of pathology. We compared membrane-associated, sodium dodecyl sulfate-soluble α-synuclein, both the full-length 17 kDa and high molecular weight species, by western blotting in autopsied brain of patients with Parkinson's disease (brainstem-predominant Lewy body disease: n=9), multiple system atrophy (n=11), progressive supranuclear palsy (n = 16), and of normal controls (n = 13). Brain of a patient with familial Parkinsonism-dementia due to α-synuclein locus triplication (as positive control) showed increased membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels with abundant high molecular weight immunoreactivity. In multiple system atrophy, a massive increase in 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein was observed in highly pathologically affected regions, including putamen (+1760%, range +625-2900%), substantia nigra [+1000% (+356-1850%)], and white matter of internal capsule [+2210% (+430-6830%)] together with numerous high molecular weight species. Levels of 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were only modestly increased in less affected areas (cerebellar cortex, +95%; caudate, +30%; with both also showing numerous high molecular weight species) and were generally normal in cerebral cortices. In both Parkinson's disease and progressive supranuclear palsy, membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels were normal in putamen and frontal cortex whereas a trend was observed for variably increased 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synudein concentrations [+184% (-60% to +618%)] with additional high molecular weight species in Parkinson's disease substantia nigra. No obvious correlation was observed between nigral membrane-associated, sodium dodecyl sulfate-soluble (α-synuclein accumulation and Lewy body density in Parkinson's disease. Two progressive supranuclear palsy cases had membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in substantia nigra similar to multiple system atrophy. Several Parkinson's disease patients had very modest high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in putamen. Levels of 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were generally positively correlated with those of high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein and there was a trend for a positive correlation between striatal dopamine loss and 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein concentrations in multiple system atrophy. Brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulations in Parkinson's disease and multiple system atrophy are regionally specific, suggesting that these sporadic α-synucleinopathies, unlike familial Parkinsonism-dementia, are not associated with a simple global over-expression of the protein. Despite a similar extent of dopamine depletion, the magnitude of brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein changes is disease specific, with multiple system atrophy clearly having the most severe accumulation. Literature discrepancies on α-synuclein status in 'Parkinson's disease' might be explained by inclusion of cases not having classic brainstem-predominant Lewy body disease and by variable α-synuclein accumulation within this diagnostic classification. |
| CC : | 002B17; 002B17F |
| FD : | Atrophie multisystématisée; Maladie de Parkinson; Pathologie du système nerveux; Encéphale; Méthode immunoblotting |
| FG : | Système nerveux central; Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du système nerveux central |
| ED : | Multiple system atrophy; Parkinson disease; Nervous system diseases; Encephalon; Immunoblotting assay |
| EG : | Central nervous system; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease |
| SD : | Atrofia multisistematizada; Parkinson enfermedad; Sistema nervioso patología; Encéfalo; Western blotting |
| LO : | INIST-998.354000189974790140 |
| ID : | 10-0060219 |
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Kish</name><affiliation><inist:fA14 i1="02"><s1>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name><affiliation><inist:fA14 i1="09"><s1>Center for Brain Research, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Furukawa, Yoshiaki" sort="Furukawa, Yoshiaki" uniqKey="Furukawa Y" first="Yoshiaki" last="Furukawa">Yoshiaki Furukawa</name><affiliation><inist:fA14 i1="01"><s1>Movement Disorders Research Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="10"><s1>Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>11 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="11"><s1>Department of Neurology, Faculty of Medicine, University & Post Graduate University of Juntendo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0060219</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0060219 INIST</idno><idno type="RBID">Pascal:10-0060219</idno><idno type="wicri:Area/PascalFrancis/Corpus">000469</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation</title><author><name sortKey="Junchao Tong" sort="Junchao Tong" uniqKey="Junchao Tong" last="Junchao Tong">JUNCHAO TONG</name><affiliation><inist:fA14 i1="01"><s1>Movement Disorders Research Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Wong, Henry" sort="Wong, Henry" uniqKey="Wong H" first="Henry" last="Wong">Henry Wong</name><affiliation><inist:fA14 i1="01"><s1>Movement Disorders Research Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Guttman, Mark" sort="Guttman, Mark" uniqKey="Guttman M" first="Mark" last="Guttman">Mark Guttman</name><affiliation><inist:fA14 i1="02"><s1>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Centre for Movement Disorders</s1><s2>Markham, Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ang, Lee C" sort="Ang, Lee C" uniqKey="Ang L" first="Lee C." last="Ang">Lee C. Ang</name><affiliation><inist:fA14 i1="04"><s1>Department of Pathology, University of Western Ontario</s1><s2>London, Ontario</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Forno, Lysia S" sort="Forno, Lysia S" uniqKey="Forno L" first="Lysia S." last="Forno">Lysia S. Forno</name><affiliation><inist:fA14 i1="05"><s1>Department of Pathology, VA Palo Alto Health Care System</s1><s2>Palo Alto, CA</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Shimadzu, Mitsunobu" sort="Shimadzu, Mitsunobu" uniqKey="Shimadzu M" first="Mitsunobu" last="Shimadzu">Mitsunobu Shimadzu</name><affiliation><inist:fA14 i1="06"><s1>Mitsubishi Chemical Medience Corporation</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation><inist:fA14 i1="07"><s1>Division of Neurology, University of Saskatchewan</s1><s2>Saskatoon, Saskatchewan</s2><s3>CAN</s3><sZ>7 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Muenter, Manfred D" sort="Muenter, Manfred D" uniqKey="Muenter M" first="Manfred D." last="Muenter">Manfred D. Muenter</name><affiliation><inist:fA14 i1="08"><s1>Department of Neurology, Mayo Clinic Scottsdale</s1><s2>Scottsdale, AZ</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Kish, Stephen J" sort="Kish, Stephen J" uniqKey="Kish S" first="Stephen J." last="Kish">Stephen J. Kish</name><affiliation><inist:fA14 i1="02"><s1>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name><affiliation><inist:fA14 i1="09"><s1>Center for Brain Research, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Furukawa, Yoshiaki" sort="Furukawa, Yoshiaki" uniqKey="Furukawa Y" first="Yoshiaki" last="Furukawa">Yoshiaki Furukawa</name><affiliation><inist:fA14 i1="01"><s1>Movement Disorders Research Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="10"><s1>Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>11 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="11"><s1>Department of Neurology, Faculty of Medicine, University & Post Graduate University of Juntendo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Encephalon</term><term>Immunoblotting assay</term><term>Multiple system atrophy</term><term>Nervous system diseases</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Atrophie multisystématisée</term><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Encéphale</term><term>Méthode immunoblotting</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">α-synuclein is a major component of Lewy bodies and glial cytoplasmic inclusions, pathological hallmarks of idiopathic Parkinson's disease and multiple system atrophy, and it is assumed to be aetiologically involved in these conditions. However, the quantitative status of brain α-synuclein in different Parkinsonian disorders is still unresolved and it is uncertain whether α-synuclein accumulation is restricted to regions of pathology. We compared membrane-associated, sodium dodecyl sulfate-soluble α-synuclein, both the full-length 17 kDa and high molecular weight species, by western blotting in autopsied brain of patients with Parkinson's disease (brainstem-predominant Lewy body disease: n=9), multiple system atrophy (n=11), progressive supranuclear palsy (n = 16), and of normal controls (n = 13). Brain of a patient with familial Parkinsonism-dementia due to α-synuclein locus triplication (as positive control) showed increased membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels with abundant high molecular weight immunoreactivity. In multiple system atrophy, a massive increase in 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein was observed in highly pathologically affected regions, including putamen (+1760%, range +625-2900%), substantia nigra [+1000% (+356-1850%)], and white matter of internal capsule [+2210% (+430-6830%)] together with numerous high molecular weight species. Levels of 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were only modestly increased in less affected areas (cerebellar cortex, +95%; caudate, +30%; with both also showing numerous high molecular weight species) and were generally normal in cerebral cortices. In both Parkinson's disease and progressive supranuclear palsy, membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels were normal in putamen and frontal cortex whereas a trend was observed for variably increased 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synudein concentrations [+184% (-60% to +618%)] with additional high molecular weight species in Parkinson's disease substantia nigra. No obvious correlation was observed between nigral membrane-associated, sodium dodecyl sulfate-soluble (α-synuclein accumulation and Lewy body density in Parkinson's disease. Two progressive supranuclear palsy cases had membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in substantia nigra similar to multiple system atrophy. Several Parkinson's disease patients had very modest high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in putamen. Levels of 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were generally positively correlated with those of high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein and there was a trend for a positive correlation between striatal dopamine loss and 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein concentrations in multiple system atrophy. Brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulations in Parkinson's disease and multiple system atrophy are regionally specific, suggesting that these sporadic α-synucleinopathies, unlike familial Parkinsonism-dementia, are not associated with a simple global over-expression of the protein. Despite a similar extent of dopamine depletion, the magnitude of brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein changes is disease specific, with multiple system atrophy clearly having the most severe accumulation. Literature discrepancies on α-synuclein status in 'Parkinson's disease' might be explained by inclusion of cases not having classic brainstem-predominant Lewy body disease and by variable α-synuclein accumulation within this diagnostic classification.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0006-8950</s0></fA01><fA03 i2="1"><s0>Brain</s0></fA03><fA05><s2>133</s2></fA05><fA06><s3>p. 1</s3></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation</s1></fA08><fA11 i1="01" i2="1"><s1>JUNCHAO TONG</s1></fA11><fA11 i1="02" i2="1"><s1>WONG (Henry)</s1></fA11><fA11 i1="03" i2="1"><s1>GUTTMAN (Mark)</s1></fA11><fA11 i1="04" i2="1"><s1>ANG (Lee C.)</s1></fA11><fA11 i1="05" i2="1"><s1>FORNO (Lysia S.)</s1></fA11><fA11 i1="06" i2="1"><s1>SHIMADZU (Mitsunobu)</s1></fA11><fA11 i1="07" i2="1"><s1>RAJPUT (Ali H.)</s1></fA11><fA11 i1="08" i2="1"><s1>MUENTER (Manfred D.)</s1></fA11><fA11 i1="09" i2="1"><s1>KISH (Stephen J.)</s1></fA11><fA11 i1="10" i2="1"><s1>HORNYKIEWICZ (Oleh)</s1></fA11><fA11 i1="11" i2="1"><s1>FURUKAWA (Yoshiaki)</s1></fA11><fA14 i1="01"><s1>Movement Disorders Research Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="02"><s1>Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="03"><s1>Centre for Movement Disorders</s1><s2>Markham, Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Pathology, University of Western Ontario</s1><s2>London, Ontario</s2><s3>CAN</s3><sZ>4 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Pathology, VA Palo Alto Health Care System</s1><s2>Palo Alto, CA</s2><s3>USA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Mitsubishi Chemical Medience Corporation</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>6 aut.</sZ></fA14><fA14 i1="07"><s1>Division of Neurology, University of Saskatchewan</s1><s2>Saskatoon, Saskatchewan</s2><s3>CAN</s3><sZ>7 aut.</sZ></fA14><fA14 i1="08"><s1>Department of Neurology, Mayo Clinic Scottsdale</s1><s2>Scottsdale, AZ</s2><s3>USA</s3><sZ>8 aut.</sZ></fA14><fA14 i1="09"><s1>Center for Brain Research, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>10 aut.</sZ></fA14><fA14 i1="10"><s1>Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>11 aut.</sZ></fA14><fA14 i1="11"><s1>Department of Neurology, Faculty of Medicine, University & Post Graduate University of Juntendo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>11 aut.</sZ></fA14><fA20><s1>172-188</s1></fA20><fA21><s1>2010</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>998</s2><s5>354000189974790140</s5></fA43><fA44><s0>0000</s0><s1>© 2010 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>2 p.1/2</s0></fA45><fA47 i1="01" i2="1"><s0>10-0060219</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Brain</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>α-synuclein is a major component of Lewy bodies and glial cytoplasmic inclusions, pathological hallmarks of idiopathic Parkinson's disease and multiple system atrophy, and it is assumed to be aetiologically involved in these conditions. However, the quantitative status of brain α-synuclein in different Parkinsonian disorders is still unresolved and it is uncertain whether α-synuclein accumulation is restricted to regions of pathology. We compared membrane-associated, sodium dodecyl sulfate-soluble α-synuclein, both the full-length 17 kDa and high molecular weight species, by western blotting in autopsied brain of patients with Parkinson's disease (brainstem-predominant Lewy body disease: n=9), multiple system atrophy (n=11), progressive supranuclear palsy (n = 16), and of normal controls (n = 13). Brain of a patient with familial Parkinsonism-dementia due to α-synuclein locus triplication (as positive control) showed increased membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels with abundant high molecular weight immunoreactivity. In multiple system atrophy, a massive increase in 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein was observed in highly pathologically affected regions, including putamen (+1760%, range +625-2900%), substantia nigra [+1000% (+356-1850%)], and white matter of internal capsule [+2210% (+430-6830%)] together with numerous high molecular weight species. Levels of 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were only modestly increased in less affected areas (cerebellar cortex, +95%; caudate, +30%; with both also showing numerous high molecular weight species) and were generally normal in cerebral cortices. In both Parkinson's disease and progressive supranuclear palsy, membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels were normal in putamen and frontal cortex whereas a trend was observed for variably increased 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synudein concentrations [+184% (-60% to +618%)] with additional high molecular weight species in Parkinson's disease substantia nigra. No obvious correlation was observed between nigral membrane-associated, sodium dodecyl sulfate-soluble (α-synuclein accumulation and Lewy body density in Parkinson's disease. Two progressive supranuclear palsy cases had membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in substantia nigra similar to multiple system atrophy. Several Parkinson's disease patients had very modest high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in putamen. Levels of 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were generally positively correlated with those of high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein and there was a trend for a positive correlation between striatal dopamine loss and 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein concentrations in multiple system atrophy. Brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulations in Parkinson's disease and multiple system atrophy are regionally specific, suggesting that these sporadic α-synucleinopathies, unlike familial Parkinsonism-dementia, are not associated with a simple global over-expression of the protein. Despite a similar extent of dopamine depletion, the magnitude of brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein changes is disease specific, with multiple system atrophy clearly having the most severe accumulation. Literature discrepancies on α-synuclein status in 'Parkinson's disease' might be explained by inclusion of cases not having classic brainstem-predominant Lewy body disease and by variable α-synuclein accumulation within this diagnostic classification.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17F</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Atrophie multisystématisée</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Multiple system atrophy</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Atrofia multisistematizada</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Encéphale</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Encephalon</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Encéfalo</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Méthode immunoblotting</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Immunoblotting assay</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Western blotting</s0><s5>10</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Système nerveux central</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Central nervous system</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Sistema nervioso central</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>41</s5></fC07><fN21><s1>039</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 10-0060219 INIST</NO><ET>Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation</ET><AU>JUNCHAO TONG; WONG (Henry); GUTTMAN (Mark); ANG (Lee C.); FORNO (Lysia S.); SHIMADZU (Mitsunobu); RAJPUT (Ali H.); MUENTER (Manfred D.); KISH (Stephen J.); HORNYKIEWICZ (Oleh); FURUKAWA (Yoshiaki)</AU><AF>Movement Disorders Research Laboratory, Centre for Addiction and Mental Health/Toronto, Ontario/Canada (1 aut., 2 aut., 11 aut.); Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health/Toronto, Ontario/Canada (1 aut., 3 aut., 9 aut.); Centre for Movement Disorders/Markham, Ontario/Canada (3 aut.); Department of Pathology, University of Western Ontario/London, Ontario/Canada (4 aut.); Department of Pathology, VA Palo Alto Health Care System/Palo Alto, CA/Etats-Unis (5 aut.); Mitsubishi Chemical Medience Corporation/Tokyo/Japon (6 aut.); Division of Neurology, University of Saskatchewan/Saskatoon, Saskatchewan/Canada (7 aut.); Department of Neurology, Mayo Clinic Scottsdale/Scottsdale, AZ/Etats-Unis (8 aut.); Center for Brain Research, University of Vienna/Vienna/Autriche (10 aut.); Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center/Tokyo/Japon (11 aut.); Department of Neurology, Faculty of Medicine, University & Post Graduate University of Juntendo/Tokyo/Japon (11 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Brain; ISSN 0006-8950; Royaume-Uni; Da. 2010; Vol. 133; No. p. 1; Pp. 172-188; Bibl. 2 p.1/2</SO><LA>Anglais</LA><EA>α-synuclein is a major component of Lewy bodies and glial cytoplasmic inclusions, pathological hallmarks of idiopathic Parkinson's disease and multiple system atrophy, and it is assumed to be aetiologically involved in these conditions. However, the quantitative status of brain α-synuclein in different Parkinsonian disorders is still unresolved and it is uncertain whether α-synuclein accumulation is restricted to regions of pathology. We compared membrane-associated, sodium dodecyl sulfate-soluble α-synuclein, both the full-length 17 kDa and high molecular weight species, by western blotting in autopsied brain of patients with Parkinson's disease (brainstem-predominant Lewy body disease: n=9), multiple system atrophy (n=11), progressive supranuclear palsy (n = 16), and of normal controls (n = 13). Brain of a patient with familial Parkinsonism-dementia due to α-synuclein locus triplication (as positive control) showed increased membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels with abundant high molecular weight immunoreactivity. In multiple system atrophy, a massive increase in 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein was observed in highly pathologically affected regions, including putamen (+1760%, range +625-2900%), substantia nigra [+1000% (+356-1850%)], and white matter of internal capsule [+2210% (+430-6830%)] together with numerous high molecular weight species. Levels of 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were only modestly increased in less affected areas (cerebellar cortex, +95%; caudate, +30%; with both also showing numerous high molecular weight species) and were generally normal in cerebral cortices. In both Parkinson's disease and progressive supranuclear palsy, membrane-associated, sodium dodecyl sulfate-soluble α-synuclein levels were normal in putamen and frontal cortex whereas a trend was observed for variably increased 17 kDa membrane-associated, sodium dodecyl sulfate-soluble α-synudein concentrations [+184% (-60% to +618%)] with additional high molecular weight species in Parkinson's disease substantia nigra. No obvious correlation was observed between nigral membrane-associated, sodium dodecyl sulfate-soluble (α-synuclein accumulation and Lewy body density in Parkinson's disease. Two progressive supranuclear palsy cases had membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in substantia nigra similar to multiple system atrophy. Several Parkinson's disease patients had very modest high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulation in putamen. Levels of 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein were generally positively correlated with those of high molecular weight membrane-associated, sodium dodecyl sulfate-soluble α-synuclein and there was a trend for a positive correlation between striatal dopamine loss and 17-kDa membrane-associated, sodium dodecyl sulfate-soluble α-synuclein concentrations in multiple system atrophy. Brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein accumulations in Parkinson's disease and multiple system atrophy are regionally specific, suggesting that these sporadic α-synucleinopathies, unlike familial Parkinsonism-dementia, are not associated with a simple global over-expression of the protein. Despite a similar extent of dopamine depletion, the magnitude of brain membrane-associated, sodium dodecyl sulfate-soluble α-synuclein changes is disease specific, with multiple system atrophy clearly having the most severe accumulation. Literature discrepancies on α-synuclein status in 'Parkinson's disease' might be explained by inclusion of cases not having classic brainstem-predominant Lewy body disease and by variable α-synuclein accumulation within this diagnostic classification.</EA><CC>002B17; 002B17F</CC><FD>Atrophie multisystématisée; Maladie de Parkinson; Pathologie du système nerveux; Encéphale; Méthode immunoblotting</FD><FG>Système nerveux central; Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du système nerveux central</FG><ED>Multiple system atrophy; Parkinson disease; Nervous system diseases; Encephalon; Immunoblotting assay</ED><EG>Central nervous system; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease</EG><SD>Atrofia multisistematizada; Parkinson enfermedad; Sistema nervioso patología; Encéfalo; Western blotting</SD><LO>INIST-998.354000189974790140</LO><ID>10-0060219</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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