Fig. 10

AD tau protofibril structure (modified from [26]): Schematic representation of protein backbone of the R3 + R4 protofibril unit of AD tau paired-helical filaments and straight filaments, with selected amino acid side chains. The numbering of amino acid positions is based on the 2N4R-tau isoform (NP_005901). Antiparallel β-strands are indicated by thick arrows. In AD, the protofibril adopts a compact C-shaped structure. The E2814 HVPGG binding motif (362-366; yellow) forms the tight bend between β₇ and β₈. Red arrowheads indicate predicted strong contact points to heparin [53] resulting in heparin-mediated aggregation by compaction and stabilization of the AD protofibril. Green stars indicate sequences that interact with azure A and azure B, monodemethylated derivatives of methylene blue (MB), which have anti-aggregation effects on tau by preventing fibril formation and retaining tau in monomeric form [2]