Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 22, Issue 3, Pages 839-848Publisher
IOS PRESS
DOI: 10.3233/JAD-2010-101161
Keywords
Alzheimer's disease; amyloid-beta; neurotoxicity; protein oxidation
Categories
Funding
- NIH/NIA [2PO1 AG005119]
- Alzheimer's Association
- NIH [P20-RR021945, P30-DK072476]
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR021945] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK072476] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P01AG005119] Funding Source: NIH RePORTER
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Recent studies have demonstrated a potential role for oligomeric forms of amyloid-beta (A beta) in the pathogenesis of Alzheimer's disease (AD), although it remains unclear which aspects of AD may be mediated by oligomeric A beta. In the present study, we found that primary cultures of rat cortical neurons exhibit a dose-dependent increase in cell death following A beta 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 A beta. 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 A beta toxicity in neurons. These data indicate that oligomeric A beta 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 A beta as a contributor to neuronal oxidative stress and mitochondrial disturbances in AD.
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