Impact of Abnormal Phosphorylation on the Oligomerization of Tau Repeat R2

Overall, our results suggest that abnormal phosphorylation at Ser289 and/or Ser293 accelerates the oligomerization of R2 peptides, and consequently it may promote tau aggregation. Furthermore, we also found a pSer-cation-pSer bridge formed, thus uncovering the essential role of cation ions in the oligomerization of the phosphorylated R2 repeat. Our findings suggest that phosphorylation at Ser289 and/or Ser293 should be taken into consideration when screening the inhibitors of tau oligomerization.