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An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity.
Neurobiol Dis. 2006 Sep; 23(3):669-78.ND

Abstract

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.

Authors+Show Affiliations

Center for Neuroscience and Cell Biology of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16844381

Citation

Ferreiro, Elisabete, et al. "An Endoplasmic-reticulum-specific Apoptotic Pathway Is Involved in Prion and Amyloid-beta Peptides Neurotoxicity." Neurobiology of Disease, vol. 23, no. 3, 2006, pp. 669-78.
Ferreiro E, Resende R, Costa R, et al. An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity. Neurobiol Dis. 2006;23(3):669-78.
Ferreiro, E., Resende, R., Costa, R., Oliveira, C. R., & Pereira, C. M. (2006). An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity. Neurobiology of Disease, 23(3), 669-78.
Ferreiro E, et al. An Endoplasmic-reticulum-specific Apoptotic Pathway Is Involved in Prion and Amyloid-beta Peptides Neurotoxicity. Neurobiol Dis. 2006;23(3):669-78. PubMed PMID: 16844381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity. AU - Ferreiro,Elisabete, AU - Resende,Rosa, AU - Costa,Rui, AU - Oliveira,Catarina R, AU - Pereira,Cláudia M F, Y1 - 2006/07/17/ PY - 2006/01/12/received PY - 2006/04/05/revised PY - 2006/05/22/accepted PY - 2006/7/18/pubmed PY - 2006/11/2/medline PY - 2006/7/18/entrez SP - 669 EP - 78 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 23 IS - 3 N2 - 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. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/16844381/An_endoplasmic_reticulum_specific_apoptotic_pathway_is_involved_in_prion_and_amyloid_beta_peptides_neurotoxicity_ DB - PRIME DP - Unbound Medicine ER -