000136596 001__ 136596
000136596 005__ 20240321220113.0
000136596 0247_ $$2doi$$a10.1371/journal.pone.0042545
000136596 0247_ $$2pmid$$apmid:22880029
000136596 0247_ $$2pmc$$apmc:PMC3411845
000136596 037__ $$aDZNE-2020-02918
000136596 041__ $$aEnglish
000136596 082__ $$a610
000136596 1001_ $$0P:(DE-HGF)0$$aSchmidt, Felix$$b0
000136596 245__ $$aSingle-channel electrophysiology reveals a distinct and uniform pore complex formed by α-synuclein oligomers in lipid membranes.
000136596 260__ $$aSan Francisco, California, US$$bPLOS$$c2012
000136596 264_1 $$2Crossref$$3online$$bPublic Library of Science (PLoS)$$c2012-08-03
000136596 3367_ $$2DRIVER$$aarticle
000136596 3367_ $$2DataCite$$aOutput Types/Journal article
000136596 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1602839198_16586
000136596 3367_ $$2BibTeX$$aARTICLE
000136596 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000136596 3367_ $$00$$2EndNote$$aJournal Article
000136596 520__ $$aSynucleinopathies such as Parkinson's disease, multiple system atrophy and dementia with Lewy bodies are characterized by deposition of aggregated α-synuclein. Recent findings indicate that pathological oligomers rather than fibrillar aggregates may represent the main toxic protein species. It has been shown that α-synuclein oligomers can increase the conductance of lipid bilayers and, in cell-culture, lead to calcium dyshomeostasis and cell death. In this study, employing a setup for single-channel electrophysiology, we found that addition of iron-induced α-synuclein oligomers resulted in quantized and stepwise increases in bilayer conductance indicating insertion of distinct transmembrane pores. These pores switched between open and closed states depending on clamped voltage revealing a single-pore conductance comparable to that of bacterial porins. Pore conductance was dependent on transmembrane potential and the available cation. The pores stably inserted into the bilayer and could not be removed by buffer exchange. Pore formation could be inhibited by co-incubation with the aggregation inhibitor baicalein. Our findings indicate that iron-induced α-synuclein oligomers can form a uniform and distinct pore species with characteristic electrophysiological properties. Pore formation could be a critical event in the pathogenesis of synucleinopathies and provide a novel structural target for disease-modifying therapy.
000136596 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000136596 542__ $$2Crossref$$i2012-08-03$$uhttp://creativecommons.org/licenses/by/4.0/
000136596 588__ $$aDataset connected to CrossRef, PubMed,
000136596 650_7 $$2NLM Chemicals$$aCations
000136596 650_7 $$2NLM Chemicals$$aLipid Bilayers
000136596 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000136596 650_2 $$2MeSH$$aCations
000136596 650_2 $$2MeSH$$aElectric Conductivity
000136596 650_2 $$2MeSH$$aElectrophysiological Phenomena
000136596 650_2 $$2MeSH$$aHumans
000136596 650_2 $$2MeSH$$aLipid Bilayers: metabolism
000136596 650_2 $$2MeSH$$aModels, Biological
000136596 650_2 $$2MeSH$$aPorosity
000136596 650_2 $$2MeSH$$aProtein Structure, Quaternary
000136596 650_2 $$2MeSH$$aTime Factors
000136596 650_2 $$2MeSH$$aalpha-Synuclein: chemistry
000136596 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000136596 7001_ $$0P:(DE-HGF)0$$aLevin, Johannes$$b1
000136596 7001_ $$0P:(DE-2719)2812549$$aKamp, Frits$$b2$$udzne
000136596 7001_ $$0P:(DE-HGF)0$$aKretzschmar, Hans$$b3
000136596 7001_ $$0P:(DE-HGF)0$$aGiese, Armin$$b4$$eCorresponding author
000136596 7001_ $$0P:(DE-HGF)0$$aBötzel, Kai$$b5
000136596 77318 $$2Crossref$$3journal-article$$a10.1371/journal.pone.0042545$$b : Public Library of Science (PLoS), 2012-08-03$$n8$$pe42545$$tPLoS ONE$$v7$$x1932-6203$$y2012
000136596 773__ $$0PERI:(DE-600)2267670-3$$a10.1371/journal.pone.0042545$$gVol. 7, no. 8, p. e42545 -$$n8$$pe42545$$q7:8<e42545 -$$tPLOS ONE$$v7$$x1932-6203$$y2012
000136596 8564_ $$uhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042545
000136596 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411845
000136596 8564_ $$uhttps://pub.dzne.de/record/136596/files/2659.PDF$$yOpenAccess
000136596 8564_ $$uhttps://pub.dzne.de/record/136596/files/2659.gif?subformat=icon$$xicon$$yOpenAccess
000136596 8564_ $$uhttps://pub.dzne.de/record/136596/files/2659.jpg?subformat=icon-1440$$xicon-1440$$yOpenAccess
000136596 8564_ $$uhttps://pub.dzne.de/record/136596/files/2659.jpg?subformat=icon-180$$xicon-180$$yOpenAccess
000136596 8564_ $$uhttps://pub.dzne.de/record/136596/files/2659.jpg?subformat=icon-640$$xicon-640$$yOpenAccess
000136596 909CO $$ooai:pub.dzne.de:136596$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000136596 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812549$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000136596 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0
000136596 9141_ $$y2012
000136596 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000136596 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ
000136596 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000136596 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000136596 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record
000136596 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bPLOS ONE : 2017
000136596 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal
000136596 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ
000136596 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000136596 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000136596 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000136596 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000136596 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000136596 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000136596 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000136596 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central
000136596 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000136596 9201_ $$0I:(DE-2719)1110002$$kAG Höglinger 1$$lTranslational Neurodegeneration$$x0
000136596 980__ $$ajournal
000136596 980__ $$aVDB
000136596 980__ $$aUNRESTRICTED
000136596 980__ $$aI:(DE-2719)1110002
000136596 9801_ $$aFullTexts