Author(s): Ferreiro, Elisabete ; Resende, Rosa ; Costa, Rui ; Oliveira, Catarina R. ; Pereira, Cláudia M. F.
Date: 2006
Persistent ID: https://hdl.handle.net/10316/4738
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): 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.
http://www.sciencedirect.com/science/article/B6WNK-4KF1HJF-2/1/1c70b53c2d3ffe42c231154f0fe9258a
