Cited 110 times in
On the mechanism of internalization of alpha-synuclein into microglia: roles of ganglioside GM1 and lipid raft
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김종선 | - |
dc.date.accessioned | 2015-04-24T16:41:58Z | - |
dc.date.available | 2015-04-24T16:41:58Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0022-3042 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/104006 | - |
dc.description.abstract | ALpha-synuclein (alpha-syn) has been known to be a key player of the pathogenesis of Parkinson's disease and has recently been detected in extracellular biological fluids and shown to be rapidly secreted from cells. The penetration of alpha-syn into cells has also been observed. In this study, we observed that dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, a glucosyltransferase inhibitor, and proteinase K inhibited the internalization of extracellular monomeric alpha-syn into BV-2 cells, and the addition of monosialoganglioside GM1 ameliorated the inhibition of alpha-syn internalization in dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-treated BV-2 cells. Furthermore, inhibition of clathrin-, caveolae-, and dynamin-dependent endocytosis did not prevent the internalization of alpha-syn, but disruption of lipid raft inhibited it. Inhibition of macropinocytosis and disruption of actin and microtubule structures also did not inhibit the internalization of alpha-syn. In addition, we further confirmed these observations by co-culture system of BV-2 cells and alpha-syn-over-expressing SH-SY5Y cells. These findings suggest that extracellular alpha-syn is internalized into microglia via GM1 as well as hitherto-unknown protein receptors in clathrin-, caveolae-, and dynamin-independent, but lipid raft-dependent manner. Elucidation of the mechanism involved in internalization of alpha-syn should be greatly helpful in the development of new treatments of alpha-syn-related neurodegenerative diseases. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 400~411 | - |
dc.relation.isPartOf | JOURNAL OF NEUROCHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Caveolins/drug effects | - |
dc.subject.MESH | Caveolins/metabolism | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Clathrin/drug effects | - |
dc.subject.MESH | Clathrin/metabolism | - |
dc.subject.MESH | Coculture Techniques | - |
dc.subject.MESH | Dynamins/drug effects | - |
dc.subject.MESH | Dynamins/metabolism | - |
dc.subject.MESH | Encephalitis/metabolism | - |
dc.subject.MESH | Encephalitis/physiopathology | - |
dc.subject.MESH | Endocytosis/drug effects | - |
dc.subject.MESH | Endocytosis/physiology* | - |
dc.subject.MESH | Endopeptidase K/metabolism | - |
dc.subject.MESH | Endopeptidase K/pharmacology | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology | - |
dc.subject.MESH | Extracellular Space/drug effects | - |
dc.subject.MESH | Extracellular Space/metabolism | - |
dc.subject.MESH | G(M1) Ganglioside/metabolism* | - |
dc.subject.MESH | G(M1) Ganglioside/pharmacology | - |
dc.subject.MESH | Glucosyltransferases/antagonists & inhibitors | - |
dc.subject.MESH | Glucosyltransferases/metabolism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Membrane Microdomains/drug effects | - |
dc.subject.MESH | Membrane Microdomains/metabolism* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Microglia/drug effects | - |
dc.subject.MESH | Microglia/metabolism* | - |
dc.subject.MESH | Neurodegenerative Diseases/metabolism | - |
dc.subject.MESH | Neurodegenerative Diseases/physiopathology | - |
dc.subject.MESH | Parkinson Disease/metabolism | - |
dc.subject.MESH | Parkinson Disease/physiopathology | - |
dc.subject.MESH | Protein Transport/drug effects | - |
dc.subject.MESH | Protein Transport/physiology | - |
dc.subject.MESH | alpha-Synuclein/metabolism* | - |
dc.title | On the mechanism of internalization of alpha-synuclein into microglia: roles of ganglioside GM1 and lipid raft | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Microbiology (미생물학) | - |
dc.contributor.googleauthor | Ji-Young Park | - |
dc.contributor.googleauthor | Kwang Soo Kim | - |
dc.contributor.googleauthor | Saet-Byul Lee | - |
dc.contributor.googleauthor | Jae-Sung Ryu | - |
dc.contributor.googleauthor | Kwang Chul Chung | - |
dc.contributor.googleauthor | Young-Kug Choo | - |
dc.contributor.googleauthor | Ilo Jou | - |
dc.contributor.googleauthor | Jongsun Kim | - |
dc.contributor.googleauthor | Sang Myun Park | - |
dc.identifier.doi | 10.1111/j.1471-4159.2009.06150.x | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00921 | - |
dc.relation.journalcode | J01620 | - |
dc.identifier.eissn | 1471-4159 | - |
dc.identifier.pmid | 19457104 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2009.06150.x/abstract | - |
dc.subject.keyword | [alpha]-synuclein | - |
dc.subject.keyword | endocytosis | - |
dc.subject.keyword | gangliosides | - |
dc.subject.keyword | lipid raft | - |
dc.subject.keyword | microglia | - |
dc.contributor.alternativeName | Kim, Jong Sun | - |
dc.contributor.affiliatedAuthor | Kim, Jong Sun | - |
dc.citation.volume | 110 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 400 | - |
dc.citation.endPage | 411 | - |
dc.identifier.bibliographicCitation | JOURNAL OF NEUROCHEMISTRY, Vol.110(1) : 400-411, 2009 | - |
dc.identifier.rimsid | 46762 | - |
dc.type.rims | ART | - |
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