Artículos de revistas
RyR2-mediated Ca2+ release and mitochondrial ROS generation partake in the synaptic dysfunction caused by amyloid β peptide oligomers
Fecha
2017Registro en:
Frontiers in Molecular Neuroscience, Volumen 10,
16625099
10.3389/fnmol.2017.00115
Autor
San Martín Rovirosa, Carol
Veloso, Pablo
Adasme, Tatiana
Lobos, Pedro
Bruna, Barbara
Galaz, Jose
García, Alejandra
Hartel, Steffen
Hidalgo Tapia, María Cecilia
Paula Lima, Andrea
Institución
Resumen
© 2017 SanMartín, Veloso, Adasme, Lobos, Bruna, Galaz, García, Hartel, Hidalgo and Paula-Lima. Amyloid β peptide oligomers (AβOs), toxic aggregates with pivotal roles in Alzheimer’s disease, trigger persistent and low magnitude Ca2+ signals in neurons. We reported previously that these Ca2+ signals, which arise from Ca2+ entry and subsequent amplification by Ca2+ release through ryanodine receptor (RyR) channels, promote mitochondrial network fragmentation and reduce RyR2 expression. Here, we examined if AβOs, by inducing redox sensitive RyR-mediated Ca2+ release, stimulate mitochondrial Ca2+ -uptake, ROS generation and mitochondrial fragmentation, and also investigated the effects of the antioxidant N-acetyl cysteine (NAC) and the mitochondrial antioxidant EUK-134 on AβOs-induced mitochondrial dysfunction. In addition, we studied the contribution of the RyR2 isoform to AβOs-induced Ca2+ release, mitochondrial Ca2+ uptake and fragmentation. We show here that inhibition of NADPH oxidase