Alginate-Derived Mannuronate Oligosaccharide Attenuates Tauopathy through Enhancing Autophagy

Polymannuronate (PM) is an acidic polysaccharide prepared from alginate, contained in edible brown seaweeds. An unsaturated mannuronate oligosaccharide (MOS) is an enzymatically depolymerized oligosaccharide prepared from PM. The effects of MOS on attenuating tauopathy were studied in HEK293/Tau cells and primary triple transgenic (3xTg) neurons. MOS inhibited heparin-induced aggregation of the Tau-K18 oligomer and suppressed the levels of phosphorylated Tau protein. MOS treatment reduced the activity of glycogen synthase kinase-3 beta (GSK-3 beta) by decreasing its phosphorylation levels on the sites of Y216 and increasing phosphorylation levels on the sites of S9. MOS treatment increased the ratio of LC3-II/LC3-I levels and reduced the expression of p62, indicating an increase in autophagy. Finally, MOS-induced decrease in Tau protein expression was attenuated by the addition of an autophagy inhibitor, confirming the involvement of autophagy. These data support MOS as a promising functional food or potential pharmaceutics for attenuating Tau protein-related disease.