FIGURE 2.

Detachment of tau protein from MTs. The full-length tau protein binds to MTs, stabilizing them under the regulation of phosphatases (e.g., PP1, PP2A, PP2B, PP2C, and PP5). When tau protein phosphorylates, tau protein will detach from MTs. The microtubules will destabilize and dissociate. Detached tau fragments form tau aggregation, which ultimately leads to the formation of NFTs. At the same time, phosphorylated tau protein and detached tau fragments misfold and form tau oligomers, which are the precursors of NFTs, or toxic tau seeds.