HS3ST2 expression is critical for the abnormal phosphorylation of tau in Alzheimer’s disease-related tau pathology

This study investigates the role of HS3ST2, an enzyme that modifies heparan sulphates, in the abnormal phosphorylation of tau protein, a hallmark of Alzheimer's disease. The researchers found that HS3ST2 is more abundant in the brains of Alzheimer's patients. They also discovered that 3-O-sulphated heparan sulphates, produced by HS3ST2, can interact with tau inside cells, leading to its abnormal phosphorylation. In a zebrafish model of tauopathy, inhibiting HS3ST2 reduced the abnormal phosphorylation of tau and improved motor function, suggesting that HS3ST2 could be a potential therapeutic target for Alzheimer's disease.

• 1
  HS3ST2 expression is increased in the hippocampus of Alzheimer's disease patients compared to age-matched controls.
• 2
  3-O-sulphated heparan sulphates can be internalized into cells under pathological conditions, where they interact with tau and promote its abnormal phosphorylation.
• 3
  Inhibition of hs3st2 expression in a zebrafish model of tauopathy reduces abnormal tau phosphorylation and improves motor function.