Fig. 7.

Proposed model demonstrating the involvement of AEP activation in tau hyperphosphorylation in TBI. TBI induces acidosis of the brain tissue, which increases the level of active AEP and its translocation from neuronal lysosomes to the cytoplasm and the nucleus. Active AEP cleaves I₂^PP2A into amino- and carboxy-terminal fragments [38], both of which are translocated to the cytoplasm and inhibit PP2A activity [36], leading to hyperphosphorylation of tau. I₂^PP2A, inhibitor 2 of protein phosphatase 2A; I_2NTF, amino-terminal fragment of I₂^PP2A; I_2CTF, carboxy-terminal fragment of I₂^PP2A; P-tau, hyperphosphorylated tau.