Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting several million of people worldwide. Pathological changes in the AD brain include the presence of amyloid plaques, neurofibrillary tangles, loss of neurons and synapses, and oxidative damage. These changes s...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2012/735206 |
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| author | E. Ferreiro I. Baldeiras I. L. Ferreira R. O. Costa A. C. Rego C. F. Pereira C. R. Oliveira |
| author_facet | E. Ferreiro I. Baldeiras I. L. Ferreira R. O. Costa A. C. Rego C. F. Pereira C. R. Oliveira |
| author_sort | E. Ferreiro |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting several million of people worldwide. Pathological changes in the AD brain include the presence of amyloid plaques, neurofibrillary tangles, loss of neurons and synapses, and oxidative damage. These changes strongly associate with mitochondrial dysfunction and stress of the endoplasmic reticulum (ER). Mitochondrial dysfunction is intimately linked to the production of reactive oxygen species (ROS) and mitochondrial-driven apoptosis, which appear to be aggravated in the brain of AD patients. Concomitantly, mitochondria are closely associated with ER, and the deleterious crosstalk between both organelles has been shown to be involved in neuronal degeneration in AD. Stimuli that enhance expression of normal and/or folding-defective proteins activate an adaptive unfolded protein response (UPR) that, if unresolved, can cause apoptotic cell death. ER stress also induces the generation of ROS that, together with mitochondrial ROS and decreased activity of several antioxidant defenses, promotes chronic oxidative stress. In this paper we discuss the critical role of mitochondrial and ER dysfunction in oxidative injury in AD cellular and animal models, as well as in biological fluids from AD patients. Progress in developing peripheral and cerebrospinal fluid biomarkers related to oxidative stress will also be summarized. |
| format | Article |
| id | doaj-art-f162507e6c184dbca548ea0de225ed20 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-f162507e6c184dbca548ea0de225ed202025-02-03T06:11:44ZengWileyInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/735206735206Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to BiomarkersE. Ferreiro0I. Baldeiras1I. L. Ferreira2R. O. Costa3A. C. Rego4C. F. Pereira5C. R. Oliveira6Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Largo Marquês de Pombal 3004-517, Coimbra, PortugalFaculty of Medicine, University of Coimbra, Rua Larga 3004-504, Coimbra, PortugalCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, Largo Marquês de Pombal 3004-517, Coimbra, PortugalCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, Largo Marquês de Pombal 3004-517, Coimbra, PortugalCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, Largo Marquês de Pombal 3004-517, Coimbra, PortugalCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, Largo Marquês de Pombal 3004-517, Coimbra, PortugalCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, Largo Marquês de Pombal 3004-517, Coimbra, PortugalAlzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting several million of people worldwide. Pathological changes in the AD brain include the presence of amyloid plaques, neurofibrillary tangles, loss of neurons and synapses, and oxidative damage. These changes strongly associate with mitochondrial dysfunction and stress of the endoplasmic reticulum (ER). Mitochondrial dysfunction is intimately linked to the production of reactive oxygen species (ROS) and mitochondrial-driven apoptosis, which appear to be aggravated in the brain of AD patients. Concomitantly, mitochondria are closely associated with ER, and the deleterious crosstalk between both organelles has been shown to be involved in neuronal degeneration in AD. Stimuli that enhance expression of normal and/or folding-defective proteins activate an adaptive unfolded protein response (UPR) that, if unresolved, can cause apoptotic cell death. ER stress also induces the generation of ROS that, together with mitochondrial ROS and decreased activity of several antioxidant defenses, promotes chronic oxidative stress. In this paper we discuss the critical role of mitochondrial and ER dysfunction in oxidative injury in AD cellular and animal models, as well as in biological fluids from AD patients. Progress in developing peripheral and cerebrospinal fluid biomarkers related to oxidative stress will also be summarized.http://dx.doi.org/10.1155/2012/735206 |
| spellingShingle | E. Ferreiro I. Baldeiras I. L. Ferreira R. O. Costa A. C. Rego C. F. Pereira C. R. Oliveira Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers International Journal of Cell Biology |
| title | Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers |
| title_full | Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers |
| title_fullStr | Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers |
| title_full_unstemmed | Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers |
| title_short | Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers |
| title_sort | mitochondrial and endoplasmic reticulum associated oxidative stress in alzheimer s disease from pathogenesis to biomarkers |
| url | http://dx.doi.org/10.1155/2012/735206 |
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