Neuroprotective Effect of Sirt2-specific Inhibitor AK-7 Against Acute Cerebral Ischemia is P38 Activation-dependent in Mice
Neuroprotective Effect of Sirt2-specific Inhibitor AK-7 Against Acute Cerebral Ischemia is P38 Activation-dependent in Mice
复制标题
Sirt2 特异性抑制剂 AK-7 对小鼠急性脑缺血的神经保护作用依赖于 P38 激活
DOI：
10.1016/j.neuroscience.2018.01.040
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发表时间：
2018-03-15
期刊：
影响因子：
3.3
通讯作者：
Liu，Xueyuan
中科院分区：
文献类型：
--
作者：
Wu，Danhong;Lu，Wenmei;Liu，Xueyuan
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 mannerin vitroandin 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.
