The Effects Of Ethanol On ?eta-Amyloid-Induced Toxicity In C.Elegans And The Underlying Mechanisms

Alzheimer's disease(AD)is a common neurodegenerative disease.Beta-amyloid(A?)is the main component of cerebral cortical senile plaques.The accumulated A? in the brain can induce synaptic degeneration,neuron loss,and cognitive decline.Epidemiological studies have found that excessive drinking damages the function of brain and increases the incidence of AD,while moderate drinking can delay the cognitive decline of AD patients,but the detailed mechanisms are not clear.In this study,transgenic AD C.elegans models were used to study the effects of ethanol on the toxicity of A? and the underlying molecular mechanisms.It was found that ethanol(0.25%-1%)significantly inhibited A?-induced paralysis.Thioflavin S staining was used to detect the deposition of A? fibers in AD C.elegans models and it was found that ethanol(1%)treatment significantly reduced the number of A? plaques.The Dot blot was used to detect the amount of A? and it was found that ethanol reduced the level of A? by 38.4% in AD C.elegans.Further analyses of proteasome activity showed that ethanol improved proteasome activity by 64.7% in AD C.elegans.This may be the reason why ethanol reduced the accumulation and deposition of A? in AD C.elegans.It was also found that ethanol significantly reduced the levels of A?-induced reactive oxygen species(ROS)by43.1% in AD C.elegans.The results from real-time fluorescent quantitative polymerase chain reaction showed that the gene expression of ctl-1,ctl-2,ctl-3 and sod-1 was elevated in ethanol-treated AD C.elegans,so ethanol might reduce the level of oxidative stress by up-regulation of these antioxidant enzyme genes.In conclusion,moderate concentrations of ethanol can inhibit the toxicity of A?.Moreover,this inhibitory effect may be related to the fact that ethanol can promote proteasome activity,thus reducing the level of A? and A?-deposition.Ethanol may also inhibit the toxicity of A? by inhibiting A?-induced oxidative stress.Inhibition of A? toxicity may be one of the mechanisms that cause slower cognitive decline in AD patients with moderate drinking.