Mostrar el registro sencillo del ítem
dc.contributor.author
Gallea, Jose Ignacio
dc.contributor.author
Celej, Maria Soledad
dc.date.available
2018-01-02T19:51:53Z
dc.date.issued
2014-09
dc.identifier.citation
Gallea, Jose Ignacio; Celej, Maria Soledad; Structural Insights into Amyloid Oligomers of the Parkinson Disease-related Protein α-Synuclein; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 289; 39; 9-2014; 26733-26742
dc.identifier.issn
0021-9258
dc.identifier.uri
http://hdl.handle.net/11336/32041
dc.description.abstract
The presence of intraneuronal deposits mainly formed by amyloid fibrils of the presynaptic protein α-synuclein (AS) is a hallmark of Parkinson disease. Currently, neurotoxicity is attributed to prefibrillar oligomeric species rather than the insoluble aggregates, although their mechanisms of toxicity remain elusive. Structural details of the supramolecular organization of AS oligomers are critically needed to decipher the structure-toxicity relationship underlying their pathogenicity. In this study, we employed site-specific fluorescence to get a deeper insight into the internal architecture of AS oligomeric intermediates. We demonstrate that AS oligomers are ordered assemblies possessing a well defined pattern of intermolecular contacts. Some of these contacts involve regions that form the β-sheet core in the fibrillar state, although their spatial arrangement may differ in the two aggregated forms. However, even though the two termini are excluded from the fibrillar core, they are engaged in a number of intermolecular interactions within the oligomer. Therefore, substantial structural remodeling of early oligomeric interactions is essential for fibril growth. The intermolecular contacts identified in AS oligomers can serve as targets for the rational design of anti-amyloid compounds directed at preventing oligomeric interactions/reorganizations.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Biochemistry and Molecular Biology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Alpha-Synuclein (A-Synuclein)
dc.subject
Amyloid
dc.subject
Fluorescence
dc.subject
Parkinson Disease
dc.subject
Protein Aggregation
dc.subject.classification
Otras Ciencias Químicas
dc.subject.classification
Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Structural Insights into Amyloid Oligomers of the Parkinson Disease-related Protein α-Synuclein
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-12-28T17:47:35Z
dc.journal.volume
289
dc.journal.number
39
dc.journal.pagination
26733-26742
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Gallea, Jose Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
dc.description.fil
Fil: Celej, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
dc.journal.title
Journal of Biological Chemistry (online)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1074/jbc.M114.566695
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/289/39/26733
Archivos asociados