Table 1 PP2A Tau cascade modulators and their mechanism of action
From: The role of protein phosphatase 2A tau axis in traumatic brain injury therapy
PP2A and tau modulators | Compounds | Mechanisms | Experimental model |
|---|---|---|---|
Direct PP2A activator | Sodium selenite | Activate PR55 reduce phosphorylated tau increased protein phosphatase 2A activity and PR55 expression | Rats by fluid percussion injury in rats [78] |
Indirect PP2A modulator | AEP inhibitor/AENK | Decreased the AEP interaction with SET and the cytosolic SET retention, reduce tau phosphorylation | |
Direct PP2A modulator of B-subunit | Ferulic acid | Prevented the injury-induced reduction in PP2A subunit B levels | MCAO-induced animals [59] |
PP2A agonist | FTY720 | FTY720 induced PP2A activation dephosphorylation and activation of TTP | Early brain injury (EBI) rat model [83] |
Modulators of serine/threonine PP PPP3CA PPP3CB | Â | Prevent deregulation of PPP3CA PPP3CB hyperphosphorylation of tau in (CTE) | Cell lines, animal models, and post-mortem brain tissue of patients with CTE [85, 86] |
Tau target compounds | AAVrh.10anti-p-Tau | suppress p-Tau accumulation | Murine CTE model induced by TBI [93] |
Ac-tau target compounds | Cis-p-tau antibody | Blocks early cistauosis spreading of tau-mediated neurodegeneration | TBI mice with cis-p-tau [95] |
Tau target by AAV9-mediated gene delivery | Chimeric protein | (N-terminal RNA recognition domain of TDP-43, RAVER1) decrease Ac Tau | Animal models of TBI and mouse embryonic stem cells [97] |
ac-tau target | p300/CBP inhibitors | Blocking GAPDH S-nitrosylation, inhibiting p300/CBP by salsalate or diflunisal, | TBI Human and animal model [67] |
PP2A activator | Zinc chelating Agents | Upregulate PP2A chemically or genetically and alleviates zinc-induced tau hyperphosphorylation | Human-tau transgenic mice [106] |