Neuroprotective Effect of Sirt2-specific Inhibitor AK-7 Against Acute Cerebral Ischemia is P38 Activation-dependent in Mice.

Cerebral ischemia is the most common cause of stroke with high morbidity, disability and mortality. Sirtuin-2 (Sirt2), a vitally important NAD-dependent deacetylase which has been widely researched in central nervous system diseases, has also been identified as a promising treatment target using its specific inhibitors such as AK-7. In this study, we found that P38 was specifically activated after focal cerebral ischemic injury, and it was also significantly activated after AK-7 administration in a concentration-dependent manner in vitro and in vivo. AK-7 decreased the infarction volume remarkably and promoted the recovery of neurological function efficiently in the mice evaluated by behavior tests. In contrast, pP38 inhibition increased the infarct volume and exacerbated the symptoms of paralysis. Herein, we suggest AK-7 improves the outcome of brain ischemia in dependence on the P38 activation in mice, which may serve as a strategy for the treatment of stroke.