dc.contributor.author | Pountney, DL | |
dc.contributor.author | Voelcker, NH | |
dc.contributor.author | Gai, WP | |
dc.date.accessioned | 2017-05-03T15:03:36Z | |
dc.date.available | 2017-05-03T15:03:36Z | |
dc.date.issued | 2005 | |
dc.date.modified | 2009-12-15T03:14:51Z | |
dc.identifier.issn | 1029-8428 | |
dc.identifier.doi | 10.1007/BF03033776 | |
dc.identifier.uri | http://hdl.handle.net/10072/27503 | |
dc.description.abstract | Recently, 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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | F.P. Graham Publishing Co. | |
dc.publisher.place | USA | |
dc.publisher.uri | http://www.springer.com/biomed/neuroscience/journal/12640 | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 59 | |
dc.relation.ispartofpageto | 67 | |
dc.relation.ispartofissue | 1-2 | |
dc.relation.ispartofjournal | Neurotoxicity Research | |
dc.relation.ispartofvolume | 7 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearch | Neurosciences | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3202 | |
dc.subject.fieldofresearchcode | 3209 | |
dc.title | Annular alpha-synuclein oligomers are potentially toxic agents in alpha-synucleinopathy. Hypothesis. | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2005 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Pountney, Dean L. | |