000101559 001__ 101559
000101559 005__ 20230519145422.0
000101559 0247_ $$2doi$$a10.1038/s41467-021-21937-3
000101559 0248_ $$2sideral$$a123937
000101559 037__ $$aART-2021-123937
000101559 041__ $$aeng
000101559 100__ $$aCascella, R.
000101559 245__ $$aThe release of toxic oligomers from a-synuclein fibrils induces dysfunction in neuronal cells
000101559 260__ $$c2021
000101559 5060_ $$aAccess copy available to the general public$$fUnrestricted
000101559 5203_ $$aThe 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.
000101559 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000101559 590__ $$a17.694$$b2021
000101559 592__ $$a4.846$$b2021
000101559 594__ $$a23.2$$b2021
000101559 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 74 = 0.081$$c2021$$dQ1$$eT1
000101559 593__ $$aChemistry (miscellaneous)$$c2021$$dQ1
000101559 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2021$$dQ1
000101559 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000101559 700__ $$aChen, S.W.
000101559 700__ $$aBigi, A.
000101559 700__ $$0(orcid)0000-0002-7848-5373$$aCamino, J.D.$$uUniversidad de Zaragoza
000101559 700__ $$aXu, C.K.
000101559 700__ $$aDobson, C.M.
000101559 700__ $$aChiti, F.
000101559 700__ $$0(orcid)0000-0002-9138-6687$$aCremades, N.$$uUniversidad de Zaragoza
000101559 700__ $$aCecchi, C.
000101559 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000101559 773__ $$g12, 1 (2021), 1814 [16 pp]$$tNature communications$$x2041-1723
000101559 8564_ $$s10089790$$uhttps://zaguan.unizar.es/record/101559/files/texto_completo.pdf$$yVersión publicada
000101559 8564_ $$s1400147$$uhttps://zaguan.unizar.es/record/101559/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000101559 909CO $$ooai:zaguan.unizar.es:101559$$particulos$$pdriver
000101559 951__ $$a2023-05-18-14:08:24
000101559 980__ $$aARTICLE