能量代谢障碍与糖尿病脑病的发生密切相关，而作为能量代谢调节的关键酶AMPK活性降低在糖尿病脑病发病过程中起了重要作用，但AMPK如何失活仍存许多疑问。有研究表明异常激活的Cdk5通过磷酸化多种激酶参与神经退行性疾病的发生。AMPKα2 345和529位丝氨酸满足Cdk5的底物一般都具有特定S/TPXK/R序列的条件。前期我们发现，糖尿病大鼠脑内存在能量代谢障碍，Cdk5异常活化增加，AMPKα2的活性降低。据此推测：糖尿病状态下，海马神经元内活化的Cdk5能够磷酸化AMPKα2 345和529位丝氨酸，进而抑制AMPKα2的活性，参与糖尿病脑病的发病。本课题首先在体外确认Cdk5对AMPKα2 345或和529位点磷酸化的专一性，并进一步在高糖诱导的海马神经元损伤和自发性糖尿病GK大鼠模型上研究Cdk5介导的AMPKα2蛋白磷酸化在糖尿病脑病中的作用机制，为糖尿病脑病的治疗提供新的思路。

Energy metabolism dysfunction is closely related to the occurrence of diabetic encephalopathy, and as the key enzyme of energy metabolic regulation， AMPK lower activity play an important role in the pathogenesis of diabetic encephalopathy. However, the related molecular mechanisms of AMPK inactivation in the development of diabetic encephalopathy still remains unknown.Studies have shown that abnormal activation of Cdk5 is involved in neurodegenerative disease through phosphorylating multiple protein kinases. 345 and 529 - bit serine of AMPKα2 meet the condition which Cdk5 substrates have a specific sequence of S/TPXK/R. We have found that there are energy metabolism dysfunction, the abnormal activation of Cdk5 increasing and the activity of AMPKα2 reducing in diabetic rats. Therefore, we proposed the following assumption: In the condition of diabetes, the abnormal activation of Cdk5 promotes 345 and 529 - bit serine of AMPKα2 phosphorylation, thereby inhibiting the activity of AMPKα2 in hippocampus, involved in the pathogenesis of diabetic encephalopathy. The project aims to first confirm that Cdk5 promotes 345 and 529 - bit serine of AMPKα2 phosphorylation specificity in vitro, and further research the mechanism of diabetic encephalopathy on the Cdk5 mediated AMPKα2 phosphorylation on the hippocampus neuron damage induced by high sugar and spontaneous diabetic GK rats model, providing a new method for the treatment of diabetic encephalopathy.