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dc.contributor.authorPountney, DL
dc.contributor.authorVoelcker, NH
dc.contributor.authorGai, WP
dc.date.accessioned2017-05-03T15:03:36Z
dc.date.available2017-05-03T15:03:36Z
dc.date.issued2005
dc.date.modified2009-12-15T03:14:51Z
dc.identifier.issn1029-8428
dc.identifier.doi10.1007/BF03033776
dc.identifier.urihttp://hdl.handle.net/10072/27503
dc.description.abstractRecently, we demonstrated that soluble 30-50 nmsized annular a-synuclein oligomers are released by mild detergent treatment from glial cytoplasmic inclusions (GCIs) purified from multiple system atrophy brain tissue (Pountney et al., J. Neurochem. 90:502, 2004). Dynamic antibody recognition imaging using a specific anti-a-synuclein antibody confirmed that the annular structures were positive for a-synuclein. This showed that pathological a-synucleinopathy aggregates can be a source of annular a-synuclein species. In contrast to pathological a- synuclein, recombinant a-synuclein yielded only spherical oligomers after detergent treatment, indicating a greater propensity of the pathological protein to form stable annular oligomers. In vitro, we found that Ca2+ binding to monomeric a-synuclein, specifically amongst a range of different metal ions, induced the rapid formation of annular oligomers (Lowe et al., Protein Sci., 13:3245, 2004). Hence, a- synuclein speciation may also be influenced by the intracytoplasmic Ca2+ concentration. We also showed that annular a-synuclein oligomers can nucleate filament formation. We hypothesize that soluble a-synuclein annular oligomers may be cytotoxic species, either by interacting with cell membranes or components of the ubiquitin proteasome system. The equilibrium between a-synuclein species may be influenced by intracellular Ca2+ status, interaction with lipid vesicles or other factors.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherF.P. Graham Publishing Co.
dc.publisher.placeUSA
dc.publisher.urihttp://www.springer.com/biomed/neuroscience/journal/12640
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom59
dc.relation.ispartofpageto67
dc.relation.ispartofissue1-2
dc.relation.ispartofjournalNeurotoxicity Research
dc.relation.ispartofvolume7
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3209
dc.titleAnnular alpha-synuclein oligomers are potentially toxic agents in alpha-synucleinopathy. Hypothesis.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2005
gro.hasfulltextNo Full Text
gro.griffith.authorPountney, Dean L.


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