Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-24
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0895-8696
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-22
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Origins and effects of extracellular alpha-synuclein: implications in Parkinson's disease.
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
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't