Linked Life Data

15590652

Source:http://linkedlifedata.com/resource/pubmed/id/15590652

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-2-14
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5703-15
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15590652-Amino Acid Sequence, pubmed-meshheading:15590652-Animals, pubmed-meshheading:15590652-Brain, pubmed-meshheading:15590652-Cattle, pubmed-meshheading:15590652-Cells, Cultured, pubmed-meshheading:15590652-Cloning, Molecular, pubmed-meshheading:15590652-Cytoplasm, pubmed-meshheading:15590652-Dementia, pubmed-meshheading:15590652-Humans, pubmed-meshheading:15590652-Lewy Bodies, pubmed-meshheading:15590652-Molecular Sequence Data, pubmed-meshheading:15590652-Nerve Tissue Proteins, pubmed-meshheading:15590652-Neurites, pubmed-meshheading:15590652-Neurodegenerative Diseases, pubmed-meshheading:15590652-Neuroglia, pubmed-meshheading:15590652-Peptide Fragments, pubmed-meshheading:15590652-Protein Binding, pubmed-meshheading:15590652-Rats, pubmed-meshheading:15590652-Synucleins, pubmed-meshheading:15590652-Trypsin, pubmed-meshheading:15590652-alpha-Synuclein
pubmed:year
2005
pubmed:articleTitle
p25alpha Stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathies.
pubmed:affiliation
Institute of Medical Biochemistry and Stereological Research and Electron Microscopy Laboratory, University of Aarhus, Aarhus, DK-8000, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't