106737 20210827115915.0 doi 10.1242/jcs.180737 sideral 124698 ART-2016-124698 eng Angelova, P.R. Ca2+ is a key factor in a-synuclein-induced neurotoxicity 2016 Aggregation of α-synuclein leads to the formation of oligomeric intermediates that can interact with membranes to form pores. However, it is unknown how this leads to cell toxicity in Parkinson's disease. We investigated the species-specific effects of α-synuclein on Ca2+ signalling in primary neurons and astrocytes using live neuronal imaging and electrophysiology on artificial membranes. We demonstrate that α-synuclein induces an increase in basal intracellular Ca2+ in its unfolded monomeric state as well as in its oligomeric state. Electrophysiology of artificial membranes demonstrated that α-synuclein monomers induce irregular ionic currents, whereas α-synuclein oligomers induce rare discrete channel formation events. Despite the ability of monomeric α-synuclein to affect Ca2+ signalling, it is only the oligomeric form of α-synuclein that induces cell death. Oligomer-induced cell death was abolished by the exclusion of extracellular Ca2+, which prevented the α-synuclein-induced Ca2+ dysregulation. The findings of this study confirm that α-synuclein interacts with membranes to affect Ca2+ signalling in a structure-specific manner and the oligomeric β-sheet-rich α-synuclein species ultimately leads to Ca2+ dysregulation and Ca2+-dependent cell death. Access copy available to the general public Unrestricted info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.431 2016 CELL BIOLOGY 61 / 189 = 0.323 2016 Q2 T1 3.12 2016 Cell Biology 2016 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Ludtmann, M.H.R. Horrocks, M.H. Negoda, A. Cremades, N. Universidad de Zaragoza (orcid)0000-0002-9138-6687 Klenerman, D. Dobson, C.M. Wood, N.W. Pavlov, E.V. Gandhi, S. Abramov, A.Y. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 129, 9 (2016), 1792-1801 J. Cell Sci. JOURNAL OF CELL SCIENCE 0021-9533 2318696 http://zaguan.unizar.es/record/106737/files/texto_completo.pdf Versión publicada 3686315 http://zaguan.unizar.es/record/106737/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:106737 articulos driver 2021-08-27-09:55:50 ARTICLE