Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/17168
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Type: Journal article
Title: p25α stimulates α-synuclein aggregation and is co-localized with aggregated α-synuclein in α-synucleinopathies
Other Titles: p25alpha stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathies
Author: Lindersson, E.
Lundvig, D.
Petersen, C.
Madsen, P.
Nyengaard, J.
Hojrup, P.
Moos, T.
Otzen, D.
Gai, W.
Blumbergs, P.
Jensen, P.
Citation: Journal of Biological Chemistry, 2005; 280(7):5703-5715
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2005
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Evo 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 Jensen
Abstract: Aggregation 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.
Keywords: Brain; 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-Synuclein
Rights: © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
RMID: 0020052082
DOI: 10.1074/jbc.M410409200
Appears in Collections:Pathology publications

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