Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/17168
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dc.contributor.authorLindersson, E.en
dc.contributor.authorLundvig, D.en
dc.contributor.authorPetersen, C.en
dc.contributor.authorMadsen, P.en
dc.contributor.authorNyengaard, J.en
dc.contributor.authorHojrup, P.en
dc.contributor.authorMoos, T.en
dc.contributor.authorOtzen, D.en
dc.contributor.authorGai, W.en
dc.contributor.authorBlumbergs, P.en
dc.contributor.authorJensen, P.en
dc.date.issued2005en
dc.identifier.citationJournal of Biological Chemistry, 2005; 280(7):5703-5715en
dc.identifier.issn0021-9258en
dc.identifier.issn1083-351Xen
dc.identifier.urihttp://hdl.handle.net/2440/17168-
dc.description.abstractAggregation of the nerve cell protein alpha-synuclein is a characteristic of the common neurodegenerative alpha-synucleinopathies like Parkinson's disease and Lewy body dementia, and it plays a direct pathogenic role as demonstrated by early onset diseases caused by mis-sense mutations and multiplication of the alpha-synuclein gene. We investigated the existence of alpha-synuclein pro-aggregatory brain proteins whose dysregulation may contribute to disease progression, and we identified the brain-specific p25alpha as a candidate that preferentially binds to alpha-synuclein in its aggregated state. Functionally, purified recombinant human p25alpha strongly stimulates the aggregation of alpha-synuclein in vitro as demonstrated by thioflavin-T fluorescence and quantitative electron microscopy. p25alpha is normally only expressed in oligodendrocytes in contrast to alpha-synuclein, which is normally only expressed in neurons. This expression pattern is changed in alpha-synucleinopathies. In multiple systems atrophy, degenerating oligodendrocytes displayed accumulation of p25alpha and dystopically expressed alpha-synuclein in the glial cytoplasmic inclusions. In Parkinson's disease and Lewy body dementia, p25alpha was detectable in the neuronal Lewy body inclusions along with alpha-synuclein. The localization in alpha-synuclein-containing inclusions was verified biochemically by immunological detection in Lewy body inclusions purified from Lewy body dementia tissue and glial cytoplasmic inclusions purified from tissue from multiple systems atrophy. We suggest that p25alpha plays a pro-aggregatory role in the common neurodegenerative disorders hall-marked by alpha-synuclein aggregates.en
dc.description.statementofresponsibilityEvo Lindersson, Ditte Lundvig, Christine Petersen, Peder Madsen, Jens R. Nyengaard, Peter Højrup, Torben Moos, Daniel Otzen, Wei-Ping Gai, Peter C. Blumbergs, and Poul Henning Jensenen
dc.language.isoenen
dc.publisherAmer Soc Biochemistry Molecular Biology Incen
dc.rights© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.en
dc.subjectBrain; Neuroglia; Neurites; Lewy Bodies; Cells, Cultured; Cytoplasm; Animals; Cattle; Humans; Rats; Dementia; Neurodegenerative Diseases; Trypsin; Peptide Fragments; Nerve Tissue Proteins; Cloning, Molecular; Amino Acid Sequence; Protein Binding; Molecular Sequence Data; Synucleins; alpha-Synucleinen
dc.titlep25α stimulates α-synuclein aggregation and is co-localized with aggregated α-synuclein in α-synucleinopathiesen
dc.title.alternativep25alpha stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathiesen
dc.typeJournal articleen
dc.identifier.rmid0020052082en
dc.identifier.doi10.1074/jbc.M410409200en
dc.identifier.pubid53892-
pubs.library.collectionPathology publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Pathology publications

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