Conclusion
Our results for the first time provide evidence that HDAC6 medicated deacetylation of Prx1 and Prx2 contributes to oxidative injury in PD, suggesting that the development of specific HDAC6 inhibitor is required to develop more effective therapeutic strategies to treat PD.
Methods
We used an in vivo 6-OHDA induced PD model and a specific HDAC6 inhibitor tubastatin A to investigate the acetylation levels of peroxiredoxin1 (Prx1) and peroxiredoxin2 (Prx2) and to explore the effects of tubastain A on nigrostriatal dopaminergic system.
Objective
Histone deacetylase 6 (HDAC6) has been regarded as an unusual HDAC because of its unique properties. It contains two deacetylase catalytic domains and one ubiquitin-binding domain, thus exerting both enzymatic and non-enzymatic actions on cellular function. To date, the ubiquitin-binding activity of HDAC6 has been implicated in several neurodegenerative disorders including Parkinson's disease (PD). However, the deacetylation effect of HDAC6 in PD has not been fully illustrated. Therefore, the aim of the present study was to explore the role of deacetyation activity of HDAC6 in PD.
Results
Our results showed that expression of HDAC6 significantly increased in dopaminergic neurons after 6-OHDA injury. Acetylation levels of Prx1 and Prx2 decreased. Pharmacological inhibition of HDAC6 with specific inhibitor tubastatin A increased acetylation of Prx1 and Prx2, reduced ROS production and ameliorated dopaminergic neurotoxicity.