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On the mechanism of internalization of alpha-synuclein into microglia: roles of ganglioside GM1 and lipid raft

DC Field Value Language
dc.contributor.author김종선-
dc.date.accessioned2015-04-24T16:41:58Z-
dc.date.available2015-04-24T16:41:58Z-
dc.date.issued2009-
dc.identifier.issn0022-3042-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/104006-
dc.description.abstractALpha-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.statementOfResponsibilityopen-
dc.format.extent400~411-
dc.relation.isPartOfJOURNAL OF NEUROCHEMISTRY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCaveolins/drug effects-
dc.subject.MESHCaveolins/metabolism-
dc.subject.MESHCell Line-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHClathrin/drug effects-
dc.subject.MESHClathrin/metabolism-
dc.subject.MESHCoculture Techniques-
dc.subject.MESHDynamins/drug effects-
dc.subject.MESHDynamins/metabolism-
dc.subject.MESHEncephalitis/metabolism-
dc.subject.MESHEncephalitis/physiopathology-
dc.subject.MESHEndocytosis/drug effects-
dc.subject.MESHEndocytosis/physiology*-
dc.subject.MESHEndopeptidase K/metabolism-
dc.subject.MESHEndopeptidase K/pharmacology-
dc.subject.MESHEnzyme Inhibitors/pharmacology-
dc.subject.MESHExtracellular Space/drug effects-
dc.subject.MESHExtracellular Space/metabolism-
dc.subject.MESHG(M1) Ganglioside/metabolism*-
dc.subject.MESHG(M1) Ganglioside/pharmacology-
dc.subject.MESHGlucosyltransferases/antagonists & inhibitors-
dc.subject.MESHGlucosyltransferases/metabolism-
dc.subject.MESHHumans-
dc.subject.MESHMembrane Microdomains/drug effects-
dc.subject.MESHMembrane Microdomains/metabolism*-
dc.subject.MESHMice-
dc.subject.MESHMicroglia/drug effects-
dc.subject.MESHMicroglia/metabolism*-
dc.subject.MESHNeurodegenerative Diseases/metabolism-
dc.subject.MESHNeurodegenerative Diseases/physiopathology-
dc.subject.MESHParkinson Disease/metabolism-
dc.subject.MESHParkinson Disease/physiopathology-
dc.subject.MESHProtein Transport/drug effects-
dc.subject.MESHProtein Transport/physiology-
dc.subject.MESHalpha-Synuclein/metabolism*-
dc.titleOn the mechanism of internalization of alpha-synuclein into microglia: roles of ganglioside GM1 and lipid raft-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Microbiology (미생물학)-
dc.contributor.googleauthorJi-Young Park-
dc.contributor.googleauthorKwang Soo Kim-
dc.contributor.googleauthorSaet-Byul Lee-
dc.contributor.googleauthorJae-Sung Ryu-
dc.contributor.googleauthorKwang Chul Chung-
dc.contributor.googleauthorYoung-Kug Choo-
dc.contributor.googleauthorIlo Jou-
dc.contributor.googleauthorJongsun Kim-
dc.contributor.googleauthorSang Myun Park-
dc.identifier.doi10.1111/j.1471-4159.2009.06150.x-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00921-
dc.relation.journalcodeJ01620-
dc.identifier.eissn1471-4159-
dc.identifier.pmid19457104-
dc.identifier.urlhttp://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2009.06150.x/abstract-
dc.subject.keyword[alpha]-synuclein-
dc.subject.keywordendocytosis-
dc.subject.keywordgangliosides-
dc.subject.keywordlipid raft-
dc.subject.keywordmicroglia-
dc.contributor.alternativeNameKim, Jong Sun-
dc.contributor.affiliatedAuthorKim, Jong Sun-
dc.citation.volume110-
dc.citation.number1-
dc.citation.startPage400-
dc.citation.endPage411-
dc.identifier.bibliographicCitationJOURNAL OF NEUROCHEMISTRY, Vol.110(1) : 400-411, 2009-
dc.identifier.rimsid46762-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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