NR AVKZ
AU Ferreiro,E.; Resende,R.; Costa,R.; Oliveira,C.R.; Pereira,C.M.
TI An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity
QU Neurobiology of Disease 2006 Sep; 23(3): 669-78
PT journal article
AB Prion (PrP) and amyloid-beta (Abeta) peptides are involved in the neuronal loss that occurs in Prion disorders (PrD) and Alzheimer's disease (AD), respectively, partially due to Ca(2+) 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 Abeta peptides. In PrP106-126- and Abeta1-40-treated cortical neurons, the release of Ca(2+) through ER ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP(3)R) receptors induces ER stress and leads to increased cytosolic Ca(2+) 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 Abeta-induced perturbation of ER Ca(2+) homeostasis is a death message that leads to neuronal loss, suggesting that the regulation of ER Ca(2+) levels may be a potential therapeutical target for PrD and AD.
MH Alzheimer Disease/*metabolism/physiopathology; Amyloid beta-Protein/metabolism/*toxicity; Animals; Apoptosis/*drug effects/physiology; Calcium/metabolism; Calcium Channels/drug effects/metabolism; Calcium Signaling/drug effects/physiology; Caspases/metabolism; Cells, Cultured; Cerebral Cortex/drug effects/metabolism/physiopathology; Electron Transport Complex IV/metabolism; Endoplasmic Reticulum/*drug effects/metabolism; Homeostasis/drug effects/physiology; Neurons/drug effects/pathology; Neurotoxins/metabolism/toxicity; Oxidative Stress/drug effects/physiology; Peptide Fragments/metabolism/toxicity; Peptides/metabolism/toxicity; Prion Diseases/*metabolism/physiopathology; Prions/metabolism/*toxicity; Rats; Rats, Wistar; Reactive Oxygen Species/metabolism; Receptors, Cytoplasmic and Nuclear/drug effects/metabolism; Research Support, Non-U.S. Gov't; Ryanodine Receptor Calcium Release Channel/drug effects/metabolism
AD Center for Neuroscience and Cell Biology of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
SP englisch
PO USA