Figure 10.

Proposed pathways for PRX2 overexpression conferred neuroprotection against 6-OHDA. Based on our findings, under oxidative stress induced by 6-OHDA, PRXs are readily oxidized with a consequent reduction in antioxidative activity. Trx was oxidized in an effort to reduce the oxidized PRX. Oxidized Trx then dissociated from ASK1, leading to the activation of ASK1 and subsequent p38 and JNK apoptotic cascades. Replenishment of abundant amounts of functional deoxidized PRX2 inhibit the cysteine thiol–disulfide exchange between PRX2 and Trx and drive the PRX-Trx reaction toward the production of overoxidized PRXs, resulting in the reduction of oxidized Trx and an increase in PRX-SO₃ after PRX2 overexpression. As a consequence, more reduced Trx is available to inhibit the activation of ASK1 and related cell death events.