Source:http://linkedlifedata.com/resource/pubmed/id/17883396
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2007-12-11
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| pubmed:abstractText |
There is increasing evidence that aggregation of alpha-synuclein contributes to the functional and structural deterioration in the CNS of Parkinson's disease patients and transgenic animal models. alpha-Synuclein binds to various cellular proteins and aggregated alpha-synuclein species may affect their physiological function. In the present study, we used protein arrays spotted with 178 active human kinases for a large-scale analysis of the effects of recombinant alpha-synuclein on kinase activities. Incubation with globular alpha-synuclein oligomers significantly inhibited autophosphorylation of p21-activated kinase (PAK4) compared to treatment with monomeric alpha-synuclein or beta-synuclein. A concentration-dependent inhibition was also observed in a solution-based kinase assay. To show in vivo relevance, we analyzed brainstem protein extracts from alpha-synuclein (A30P) transgenic mice where accumulation of alpha-synuclein oligomers has been demonstrated. By immunoblotting using a phospho-specific antibody, we detected a significant decline in phosphorylation of LIM kinase 1, a physiological substrate for PAK4. Suppression of PAK activity by amyloid-beta oligomers has been reported in Alzheimer's disease. Thus, PAKs may represent a target for various neurotoxic protein oligomers, and signaling deficits may contribute to the behavioral defects in chronic neurodegenerative diseases.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Lim Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Pak4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Polymers,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Synuclein,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Synuclein,
http://linkedlifedata.com/resource/pubmed/chemical/p21-Activated Kinases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1471-4159
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
103
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2401-7
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| pubmed:meshHeading |
pubmed-meshheading:17883396-Animals,
pubmed-meshheading:17883396-Brain Stem,
pubmed-meshheading:17883396-Dose-Response Relationship, Drug,
pubmed-meshheading:17883396-Enzyme Activation,
pubmed-meshheading:17883396-Enzyme Inhibitors,
pubmed-meshheading:17883396-Female,
pubmed-meshheading:17883396-Inclusion Bodies,
pubmed-meshheading:17883396-Lim Kinases,
pubmed-meshheading:17883396-Macromolecular Substances,
pubmed-meshheading:17883396-Mice,
pubmed-meshheading:17883396-Mice, Inbred C57BL,
pubmed-meshheading:17883396-Mice, Transgenic,
pubmed-meshheading:17883396-Nerve Degeneration,
pubmed-meshheading:17883396-Neurodegenerative Diseases,
pubmed-meshheading:17883396-Neurons,
pubmed-meshheading:17883396-Phosphorylation,
pubmed-meshheading:17883396-Polymers,
pubmed-meshheading:17883396-Protein Array Analysis,
pubmed-meshheading:17883396-alpha-Synuclein,
pubmed-meshheading:17883396-beta-Synuclein,
pubmed-meshheading:17883396-p21-Activated Kinases
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| pubmed:year |
2007
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| pubmed:articleTitle |
Functional protein kinase arrays reveal inhibition of p-21-activated kinase 4 by alpha-synuclein oligomers.
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| pubmed:affiliation |
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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