Neuron Specific Toxicity of Oligomeric Amyloid-β: Role for JUN-Kinase and Oxidative Stress
| Autor: | M. Paul Murphy, Adam M. Weidner, William R. Markesbery, Harry LeVine, Annadora J. Bruce-Keller, Jeffrey N. Keller, Sun Ok Fernandez-Kim, Kalavathi Dasuri, Philip J. Ebenezer, Le Zhang, Elena Gavilán |
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| Rok vydání: | 2010 |
| Předmět: |
Cell type
Biology medicine.disease_cause Article Rats Sprague-Dawley Thiadiazoles medicine Animals Cells Cultured Neurons chemistry.chemical_classification Sulfonamides Reactive oxygen species Amyloid beta-Peptides General Neuroscience JNK Mitogen-Activated Protein Kinases General Medicine JUN kinase Molecular biology Rats Oxidative Stress Psychiatry and Mental health Clinical Psychology medicine.anatomical_structure chemistry Toxicity Mitochondrial fission Neuron Geriatrics and Gerontology Reactive Oxygen Species Neuron death Oxidative stress |
| Zdroj: | Journal of Alzheimer's Disease. 22:839-848 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Recent studies have demonstrated a potential role for oligomeric forms of beta amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD), although it remains unclear which aspects of AD may be mediated by oligomeric Aβ. In the present study we found that primary cultures of rat cortical neurons exhibit a dose-dependent increase in cell death following Aβ oligomer administration, while primary cultures of astrocytes exhibited no overt toxicity with even the highest concentrations of oligomer treatment. Neither cell type exhibited toxicity when treated by equal concentrations of monomeric Aβ. The neuron death induced by oligomer treatment was associated with an increase in reactive oxygen species (ROS), altered expression of mitochondrial fission and fusion proteins, and JUN kinase activation. Pharmacological inhibition of JUN kinase ameliorated oligomeric Aβ toxicity in neurons. These data indicate that oligomeric Aβ is sufficient to selectively induce toxicity in neurons, but not astrocytes, with neuron death occurring in a JUN kinase-dependent manner. Additionally, these observations implicate a role for oligomeric Aβ as a contributor to neuronal oxidative stress and mitochondrial disturbances in AD. |
| Databáze: | OpenAIRE |
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