101559 20230519145422.0 doi 10.1038/s41467-021-21937-3 sideral 123937 ART-2021-123937 eng Cascella, R. The release of toxic oligomers from a-synuclein fibrils induces dysfunction in neuronal cells 2021 Access copy available to the general public Unrestricted The self-assembly of a-synuclein (aS) into intraneuronal inclusion bodies is a key characteristic of Parkinson’s disease. To define the nature of the species giving rise to neuronal damage, we have investigated the mechanism of action of the main aS populations that have been observed to form progressively during fibril growth. The aS fibrils release soluble prefibrillar oligomeric species with cross-ß structure and solvent-exposed hydrophobic clusters. aS prefibrillar oligomers are efficient in crossing and permeabilize neuronal membranes, causing cellular insults. Short fibrils are more neurotoxic than long fibrils due to the higher proportion of fibrillar ends, resulting in a rapid release of oligomers. The kinetics of released aS oligomers match the observed kinetics of toxicity in cellular systems. In addition to previous evidence that aS fibrils can spread in different brain areas, our in vitro results reveal that aS fibrils can also release oligomeric species responsible for an immediate dysfunction of the neurons in the vicinity of these species. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 17.694 2021 MULTIDISCIPLINARY SCIENCES 6 / 74 = 0.081 2021 Q1 T1 4.846 2021 Chemistry (miscellaneous) 2021 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2021 Q1 23.2 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Chen, S.W. Bigi, A. Camino, J.D. Universidad de Zaragoza (orcid)0000-0002-7848-5373 Xu, C.K. Dobson, C.M. Chiti, F. Cremades, N. Universidad de Zaragoza (orcid)0000-0002-9138-6687 Cecchi, C. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 12, 1 (2021), 1814 [16 pp] Nature communications 2041-1723 10089790 http://zaguan.unizar.es/record/101559/files/texto_completo.pdf Versión publicada 1400147 http://zaguan.unizar.es/record/101559/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:101559 articulos driver 2023-05-18-14:08:24 ARTICLE