95470 20230622083310.0 doi 10.1038/s42003-020-01140-8 sideral 119524 ART-2020-119524 eng Limbocker, R. Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism 2020 Access copy available to the general public Unrestricted The 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. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 6.268 2020 BIOLOGY 8 / 93 = 0.086 2020 Q1 T1 2.811 2020 Agricultural and Biological Sciences (miscellaneous) 2020 Q1 Medicine (miscellaneous) 2020 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Mannini, B. Ruggeri, F.S. Cascella, R. Xu, C.K. Perni, M. Chia, S. Chen, S.W. Habchi, J. Bigi, A. Kreiser, R.P. Wright, A.K. Albright, J.A. Kartanas, T. Kumita, J.R. Cremades, N. Universidad de Zaragoza (orcid)0000-0002-9138-6687 Zasloff, M. Cecchi, C. Knowles, T.P.J. Chiti, F. Vendruscolo, M. Dobson, C.M. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 3, 1 (2020), 435 1-10 Communications Biology 2399-3642 1823972 http://zaguan.unizar.es/record/95470/files/texto_completo.pdf Versión publicada 72639 http://zaguan.unizar.es/record/95470/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:95470 articulos driver 2023-06-21-14:59:43 ARTICLE