The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway

• Autor(a) principal: Ferreiro, Elisabete
• Data de Publicação: 2008
• Outros Autores: Oliveira, Catarina R., Pereira, Cláudia M. F.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/4678; https://doi.org/10.1016/j.nbd.2008.02.003
• topic: Alzheimer's disease; Prion disorders; Amyloid-β; peptide; Prion peptide; Apoptosis; Ca2+ homeostasis; Endoplasmic reticulum; Mitochondria; Oxidative stress

In this study, we analyzed whether ER Ca2+ release, induced by amyloid-[beta] (A[beta]) and prion (PrP) peptides activates the mitochondrial-mediated apoptotic pathway. In cortical neurons, addition of the synthetic A[beta]1-40 or PrP106-126 peptides depletes ER Ca2+ content, leading to cytosolic Ca2+ overload. The Ca2+ released through ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP3R) receptors was shown to be involved in the loss of mitochondrial membrane potential, Bax translocation to mitochondria and apoptotic death. Our data further demonstrate that Ca2+ released from the ER leads to the depletion of endogenous GSH levels and accumulation of reactive oxygen species, which were also involved in the depolarization of the mitochondrial membrane. These results illustrate that the early A[beta]- and PrP -induced perturbation of ER Ca2+ homeostasis affects mitochondrial function, activating the mitochondrial-mediated apoptotic pathway and help to clarify the mechanism implicated in neuronal death that occurs in AD and PrD.