An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity

• Autor(a) principal: Ferreiro, Elisabete
• Data de Publicação: 2006
• Outros Autores: Resende, Rosa, Costa, Rui, 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/10316/4738; https://doi.org/10.1016/j.nbd.2006.05.011
• topic: Prion disorders; Alzheimer's disease; Prion peptide; Amyloid-β peptide; Apoptosis; Ca2+ homeostasis; Endoplasmic reticulum; Oxidative stress

Prion (PrP) and amyloid-[beta] (A[beta]) peptides are involved in the neuronal loss that occurs in Prion disorders (PrD) and Alzheimer's disease (AD), respectively, partially due to Ca2+ dysregulation. Besides, the endoplasmic reticulum (ER) stress has an active role in the neurotoxic mechanisms that lead to these pathologies. Here, we analyzed whether the ER-mediated apoptotic pathway is involved in the toxic effect of synthetic PrP and A[beta] peptides. In PrP106-126- and A[beta]1-40-treated cortical neurons, the release of Ca2+ through ER ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP3R) receptors induces ER stress and leads to increased cytosolic Ca2+ and reactive oxygen species (ROS) levels and subsequently to apoptotic death involving mitochondrial cytochrome c release and caspases activation. These results demonstrate that the early PrP- and A[beta]-induced perturbation of ER Ca2+ homeostasis is a death message that leads to neuronal loss, suggesting that the regulation of ER Ca2+ levels may be a potential therapeutical target for PrD and AD.