Abstract
Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of β-amyloid (Aβ), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early stage of AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aβ-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aβ-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aβ in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aβ by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aβ-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aβ-induced toxicity.
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