Source:http://linkedlifedata.com/resource/pubmed/id/18157654
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-12-24
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pubmed:abstractText |
Misfolding and abnormal aggregation of the neuronal protein alpha-synuclein has been implicated in the pathogenesis of Parkinson's disease and related neurological disorders, such as dementia with Lewy bodies. alpha-synuclein is a conventional cytosolic protein and is thought to exert its pathogenic function exclusively in the neuronal cytoplasm in a cell-autonomous manner. However, the current model is being challenged by a series of new observations that demonstrate the presence of alpha-synuclein and its aggregated forms in the extracellular fluid both in vivo and in vitro. Extracellular alpha-synuclein appears to be delivered by unconventional exocytosis of intravesicular alpha-synuclein, although the exact mechanism has not been characterized. Compared to the cytosolic alpha-synuclein, intravesicular alpha-synuclein is prone to aggregation and the potential source of extracellular aggregates. A number of tissue culture studies suggest that exposure to extracellular alpha-synuclein aggregates induces microglial activation, release of pro-inflammatory cytokines from astrocytes, and neurotoxicity. Thus, exocytosis of alpha-synuclein may be an important mechanism for amplifying and spreading degenerative changes from a small group of cells to its surrounding tissues, and it potentially provides therapeutic targets for halting the progression of the disease.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0895-8696
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17-22
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pubmed:meshHeading |
pubmed-meshheading:18157654-Animals,
pubmed-meshheading:18157654-Brain,
pubmed-meshheading:18157654-Encephalitis,
pubmed-meshheading:18157654-Exocytosis,
pubmed-meshheading:18157654-Extracellular Fluid,
pubmed-meshheading:18157654-Gliosis,
pubmed-meshheading:18157654-Humans,
pubmed-meshheading:18157654-Microglia,
pubmed-meshheading:18157654-Neurons,
pubmed-meshheading:18157654-Parkinson Disease,
pubmed-meshheading:18157654-alpha-Synuclein
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pubmed:year |
2008
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pubmed:articleTitle |
Origins and effects of extracellular alpha-synuclein: implications in Parkinson's disease.
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pubmed:affiliation |
Center for Geriatric Neuroscience Research, Institute of Biomedical Science and Technology, Department of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea. sjlee@konkuk.ac.kr
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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