000106737 001__ 106737 000106737 005__ 20210827115915.0 000106737 0247_ $$2doi$$a10.1242/jcs.180737 000106737 0248_ $$2sideral$$a124698 000106737 037__ $$aART-2016-124698 000106737 041__ $$aeng 000106737 100__ $$aAngelova, P.R. 000106737 245__ $$aCa2+ is a key factor in a-synuclein-induced neurotoxicity 000106737 260__ $$c2016 000106737 5060_ $$aAccess copy available to the general public$$fUnrestricted 000106737 5203_ $$aAggregation 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. 000106737 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000106737 590__ $$a4.431$$b2016 000106737 591__ $$aCELL BIOLOGY$$b61 / 189 = 0.323$$c2016$$dQ2$$eT1 000106737 592__ $$a3.12$$b2016 000106737 593__ $$aCell Biology$$c2016$$dQ1 000106737 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000106737 700__ $$aLudtmann, M.H.R. 000106737 700__ $$aHorrocks, M.H. 000106737 700__ $$aNegoda, A. 000106737 700__ $$0(orcid)0000-0002-9138-6687$$aCremades, N.$$uUniversidad de Zaragoza 000106737 700__ $$aKlenerman, D. 000106737 700__ $$aDobson, C.M. 000106737 700__ $$aWood, N.W. 000106737 700__ $$aPavlov, E.V. 000106737 700__ $$aGandhi, S. 000106737 700__ $$aAbramov, A.Y. 000106737 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000106737 773__ $$g129, 9 (2016), 1792-1801$$pJ. Cell Sci.$$tJOURNAL OF CELL SCIENCE$$x0021-9533 000106737 8564_ $$s2318696$$uhttps://zaguan.unizar.es/record/106737/files/texto_completo.pdf$$yVersión publicada 000106737 8564_ $$s3686315$$uhttps://zaguan.unizar.es/record/106737/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000106737 909CO $$ooai:zaguan.unizar.es:106737$$particulos$$pdriver 000106737 951__ $$a2021-08-27-09:55:50 000106737 980__ $$aARTICLE