000095470 001__ 95470
000095470 005__ 20230622083310.0
000095470 0247_ $$2doi$$a10.1038/s42003-020-01140-8
000095470 0248_ $$2sideral$$a119524
000095470 037__ $$aART-2020-119524
000095470 041__ $$aeng
000095470 100__ $$aLimbocker, R.
000095470 245__ $$aTrodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism
000095470 260__ $$c2020
000095470 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095470 5203_ $$aThe onset and progression of numerous protein misfolding diseases are associated with the presence of oligomers formed during the aberrant aggregation of several different proteins, including amyloid-ß (Aß) in Alzheimer’s disease and a-synuclein (aS) in Parkinson’s disease. These small, soluble aggregates are currently major targets for drug discovery. In this study, we show that trodusquemine, a naturally-occurring aminosterol, markedly reduces the cytotoxicity of aS, Aß and HypF-N oligomers to human neuroblastoma cells by displacing the oligomers from cell membranes in the absence of any substantial morphological and structural changes to the oligomers. These results indicate that the reduced toxicity results from a mechanism that is common to oligomers from different proteins, shed light on the origin of the toxicity of the most deleterious species associated with protein aggregation and suggest that aminosterols have the therapeutically-relevant potential to protect cells from the oligomer-induced cytotoxicity associated with numerous protein misfolding diseases.
000095470 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000095470 590__ $$a6.268$$b2020
000095470 591__ $$aBIOLOGY$$b8 / 93 = 0.086$$c2020$$dQ1$$eT1
000095470 592__ $$a2.811$$b2020
000095470 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2020$$dQ1
000095470 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000095470 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2020$$dQ1
000095470 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095470 700__ $$aMannini, B.
000095470 700__ $$aRuggeri, F.S.
000095470 700__ $$aCascella, R.
000095470 700__ $$aXu, C.K.
000095470 700__ $$aPerni, M.
000095470 700__ $$aChia, S.
000095470 700__ $$aChen, S.W.
000095470 700__ $$aHabchi, J.
000095470 700__ $$aBigi, A.
000095470 700__ $$aKreiser, R.P.
000095470 700__ $$aWright, A.K.
000095470 700__ $$aAlbright, J.A.
000095470 700__ $$aKartanas, T.
000095470 700__ $$aKumita, J.R.
000095470 700__ $$0(orcid)0000-0002-9138-6687$$aCremades, N.$$uUniversidad de Zaragoza
000095470 700__ $$aZasloff, M.
000095470 700__ $$aCecchi, C.
000095470 700__ $$aKnowles, T.P.J.
000095470 700__ $$aChiti, F.
000095470 700__ $$aVendruscolo, M.
000095470 700__ $$aDobson, C.M.
000095470 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000095470 773__ $$g3, 1 (2020), 435 1-10$$tCommunications Biology$$x2399-3642
000095470 8564_ $$s1823972$$uhttps://zaguan.unizar.es/record/95470/files/texto_completo.pdf$$yVersión publicada
000095470 8564_ $$s72639$$uhttps://zaguan.unizar.es/record/95470/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095470 909CO $$ooai:zaguan.unizar.es:95470$$particulos$$pdriver
000095470 951__ $$a2023-06-21-14:59:43
000095470 980__ $$aARTICLE