Source:http://linkedlifedata.com/resource/pubmed/id/18451726
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2008-5-2
|
| pubmed:abstractText |
alpha-Synuclein (alpha-syn) is the major component of pathologic inclusions that characterize neurodegenerative disorders such as Parkinson disease, dementia with Lewy body disease, and multiple system atrophy. The present study uses novel phospho-specific antibodies to assess the presence and regulation of phosphorylated Ser87 and Ser129 in alpha-syn in human brain samples and in a transgenic mouse model of alpha-synucleinopathies. By immunohistochemistry, alpha-syn phosphorylated at Ser129, but not at Ser87, was abundant in alpha-syn inclusions. Under normal conditions, Ser129 phosphorylation, but not Ser87 phosphorylation, was detected at low levels in the soluble biochemical fractions in human alpha-syn transgenic mice and stably transfected cultured cells. Therefore, a role for Ser87 phosphorylation in alpha-synucleinopathies is unlikely, and in vitro assays showed that phosphorylation at this site would inhibit polymerization. In vitro studies also indicated that hyperphosphorylation of Ser129 alpha-syn in pathologic inclusions may be due in part to the intrinsic properties of aggregated alpha-syn to act as substrates for kinases but not phosphatases. Further studies in transgenic mice and cultured cells suggest that cellular toxicity, including proteasomal dysfunction, increases casein kinase 2 activity, which results in elevated Ser129 alpha-syn phosphorylation. These data provide novel explanations for the presence of hyperphosphorylated Ser129 alpha-syn in pathologic inclusions.
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| pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/AG09215,
http://linkedlifedata.com/resource/pubmed/grant/NS053488,
http://linkedlifedata.com/resource/pubmed/grant/P01 AG009215-18,
http://linkedlifedata.com/resource/pubmed/grant/T32 AG000255-12,
http://linkedlifedata.com/resource/pubmed/grant/T32 AG00255
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0022-3069
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
67
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
402-16
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| pubmed:dateRevised |
2011-5-24
|
| pubmed:meshHeading |
pubmed-meshheading:18451726-Adult,
pubmed-meshheading:18451726-Aged,
pubmed-meshheading:18451726-Aged, 80 and over,
pubmed-meshheading:18451726-Animals,
pubmed-meshheading:18451726-Binding Sites,
pubmed-meshheading:18451726-Casein Kinase II,
pubmed-meshheading:18451726-Cell Line, Tumor,
pubmed-meshheading:18451726-Disease Models, Animal,
pubmed-meshheading:18451726-Female,
pubmed-meshheading:18451726-Humans,
pubmed-meshheading:18451726-Immunohistochemistry,
pubmed-meshheading:18451726-Inclusion Bodies,
pubmed-meshheading:18451726-Male,
pubmed-meshheading:18451726-Mice,
pubmed-meshheading:18451726-Mice, Transgenic,
pubmed-meshheading:18451726-Middle Aged,
pubmed-meshheading:18451726-Neurons,
pubmed-meshheading:18451726-Parkinson Disease,
pubmed-meshheading:18451726-Phosphorylation,
pubmed-meshheading:18451726-Proteasome Endopeptidase Complex,
pubmed-meshheading:18451726-Serine,
pubmed-meshheading:18451726-Substantia Nigra,
pubmed-meshheading:18451726-Substrate Specificity,
pubmed-meshheading:18451726-Up-Regulation,
pubmed-meshheading:18451726-alpha-Synuclein
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein.
|
| pubmed:affiliation |
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6084, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|