heparitin-sulfate and Tauopathies

Heparan sulfates have long been known to intracellularly accumulate in Alzheimer's disease neurons, where they colocalize with neurofibrillary tangles made of abnormally phosphorylated and aggregated tau protein. However, the reasons and consequences of the heparan sulfates accumulation in the Alzheimer's cells are not yet well understood. Previously, we showed that the neural heparan sulfate 3-O-sulfotransferase HS3ST2 is critical for the abnormal phosphorylation of tau in Alzheimer's disease-related tauopathy. Using cell models of tauopathy we showed that intracellular 3-O-sulfatated heparan sulfates interact with tau inducing its abnormal phosphorylation. However, it is unknown whether HS3ST2 expression induces the intracellular aggregation of tau in cells. Here, by using replicative pEBV plasmids, we engineered HEK293 cells to stably express HS3ST2 together with human tau carrying or not the P301S mutation. We show that HS3ST2 gain of function induces the cell autonomous aggregation of tau not only in cells expressing tau

Topics: Alzheimer Disease; HEK293 Cells; Heparitin Sulfate; Humans; Neurofibrillary Tangles; Phosphorylation; Sulfates; Sulfotransferases; tau Proteins; Tauopathies