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Memantine exerts neuroprotective effects by modulating alpha-synuclein transmission in a parkinsonian model

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dc.contributor.author이필휴-
dc.contributor.author이지은-
dc.contributor.author신진영-
dc.date.accessioned2022-02-23T01:23:50Z-
dc.date.available2022-02-23T01:23:50Z-
dc.date.issued2021-10-
dc.identifier.issn0014-4886-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/187676-
dc.description.abstractAmple evidence has demonstrated that α-Synuclein can propagate from one area of the brain to others via cell-to-cell transmission, which might be the underlying mechanism for pathological propagation and the disease progression of Parkinson's disease (PD). Recent reports have demonstrated cell surface receptor-mediated cell-to-cell transmission of α-synuclein. Memantine decreased the levels of internalized cytosolic α-synuclein and led to attenuation in α-synuclein-induced cell death. Specifically, memantine attenuated α-synuclein-induced expression of clathrin and EEA1, and increased expression of NR2A subunits. Moreover, memantine inhibited propagation of extracellular α-synuclein and thus, decreased the expression of the phosphorylated form of α-synuclein in dopaminergic neurons of the substantia nigra, which was accompanied by increased survival of dopaminergic neurons with functional improvement of motor deficits. The present study demonstrated that memantine modulates extracellular α-synuclein propagation by inhibiting interactions between α-synuclein and NR2A subunits, which leads to neuroprotective effects on nigral dopaminergic neurons against α-synuclein-enriched conditions. The repositioning use of memantine in α-synuclein propagation needs to be further evaluated in patients with α-synucleinopathies as an effective therapeutic approach.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherAcademic Press-
dc.relation.isPartOfEXPERIMENTAL NEUROLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHCell Line-
dc.subject.MESHHumans-
dc.subject.MESHMemantine / pharmacology*-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHNeurons / drug effects*-
dc.subject.MESHNeurons / metabolism-
dc.subject.MESHNeurons / pathology-
dc.subject.MESHNeuroprotective Agents / pharmacology*-
dc.subject.MESHParkinsonian Disorders / metabolism-
dc.subject.MESHParkinsonian Disorders / pathology*-
dc.subject.MESHReceptors, N-Methyl-D-Aspartate / drug effects-
dc.subject.MESHReceptors, N-Methyl-D-Aspartate / metabolism-
dc.subject.MESHalpha-Synuclein / drug effects*-
dc.subject.MESHalpha-Synuclein / metabolism-
dc.titleMemantine exerts neuroprotective effects by modulating alpha-synuclein transmission in a parkinsonian model-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Neurology (신경과학교실)-
dc.contributor.googleauthorJi Eun Lee-
dc.contributor.googleauthorHa Na Kim-
dc.contributor.googleauthorDong-Yeol Kim-
dc.contributor.googleauthorYu Jin Shin-
dc.contributor.googleauthorJin Young Shin-
dc.contributor.googleauthorPhil Hyu Lee-
dc.identifier.doi10.1016/j.expneurol.2021.113810-
dc.contributor.localIdA03270-
dc.relation.journalcodeJ00873-
dc.identifier.eissn1090-2430-
dc.identifier.pmid34270920-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0014488621002181?via%3Dihub-
dc.subject.keywordMemanitne-
dc.subject.keywordNR2A subunits-
dc.subject.keywordParkinson's disease-
dc.subject.keywordReceptor-mediated encodocytosis-
dc.subject.keywordTransmission-
dc.subject.keywordα-Synuclein-
dc.contributor.alternativeNameLee, Phil Hyu-
dc.contributor.affiliatedAuthor이필휴-
dc.citation.volume344-
dc.citation.startPage113810-
dc.identifier.bibliographicCitationEXPERIMENTAL NEUROLOGY, Vol.344 : 113810, 2021-10-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers

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