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

Neurobiology of Disease

Catarina R. Oliveira¹  Rosa Resende¹  Rui Costa¹  Elisabete Ferreiro¹  Cláudia M.F. Pereira² 

[1] Center for Neuroscience and Cell Biology of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal;Corresponding author. Fax: [phone].;

关键词: Prion disorders;    Alzheimer's disease;    Prion peptide;    Amyloid-β peptide;    Apoptosis;    Ca2+ homeostasis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Prion (PrP) and amyloid-β (Aβ) 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 Aβ peptides. In PrP106–126- and Aβ1–40-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 Aβ-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.

【 授权许可】

Unknown