Inhibitory Effects Of Fucoidan On Βeta-amyloid-induced Toxicity In C.elegans And The Underlying Mechanisms

Alzheimer disease(AD)is one of the most common neurodegenerative diseases.The toxicity of beta-amyloid(Aβ)plays important role in the pathogenesis of AD.In this study,we used a transgenic AD Caenorhabditis elegans(C.elegans)model to investigate the effects of fucoidan polysaccharide sulfate(FPS)on Aβ-induced pathological behaviors and the underlying molecular mechanisms.The effects of fucoidan polysaccharide sulfate on Aβ-induced paralysis were detected by worm count and Aβ deposits were determined by thioflavin S staining.The change of proteasome activity and the generation of reactive oxygen species(ROS)were studied by the detection methods of proteasome activity and ROS respectively.The level of Aβ protein and the expression of anti-oxidative stress genes were analyzed by Dot blot and real-time PCR.The results showed that fucoidan polysaccharide sulfate significantly inhibited the paralysis induced by Aβ in transgenic nematodes.Further analyses showed that fucoidan polysaccharide sulfate significantly reduced the level of Aβ and the number of Aβ plaques in AD transgenic nematodes.Aβ induced a significant decrease in proteasome activity,while fucoidan polysaccharide sulfate inhibited the lost of the proteasome activity.The level of oligomer protein had a significant reduction after treatment with fucoidan polysaccharide sulfate.Induction of Aβ resulted in a significant increase of intracellular ROS level,while fucoidan polysaccharide sulfate inhibited the increase of ROS level induced by Aβ.The real time PCR results showed that the sod-2 gene expression significantly decreased after Aβ induction,while fucoidan polysaccharide sulfate incubation significantly increased the sod-2 gene expression.In conclusion,fucoidan polysaccharide sulfate can inhibit Aβ-induced paralysis phenotype by downregulating the level of Aβ protein and reducing Aβ deposits,decreasing the levels of oligomer protein,and reducing the level of ROS.