Schizophrenia predisposition gene Unc-51-like kinase 4 for the improvement of cerebral ischemia/reperfusion injury

作者全名："Luo, Wen; Yang, Junqing"

作者地址："[Luo, Wen; Yang, Junqing] Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Luo, Wen] Third Hosp Mianyang, Dept Clin Pharm, Sichuan Mental Hlth Ctr, Mianyang 621000, Sichuan, Peoples R China"

通信作者："Yang, JQ (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China."

来源：MOLECULAR BIOLOGY REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000747082900005

JCR分区：Q4

影响因子：2.8

年份：2022

卷号：49

期号：4

开始页：2933

结束页：2943

文献类型：Article

关键词：Cerebral ischemia; reperfusion injury; ULK4; PI3K pathway; Apoptosis

摘要："Background Cerebral ischemia/reperfusion injury (CIRI) has complex pathogenesis, and inhibiting apoptosis and supporting neural progenitor proliferation are extremely beneficial strategies for treating CIRI. Unc-51-like kinase 4 (ULK4), a susceptibility gene for schizophrenia, promotes neural progenitors proliferation. The phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in CIRI via inhibition of apoptosis. Therefore, the relationship among ULK4, the PI3K pathway, and apoptosis in the context of CIRI has attracted our great interest. Methods and results Primary cortical neurons were subjected to oxygen-glucose deprivation/reperfusion (OGD/R), and rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Transfection of the ULK4-overexpression lentivirus was performed alone or in combination with PI3K inhibitor treatment. Here, we revealed that ULK4 was poorly expressed in the cortex in MCAO/R rats and OGD/R-treated primary cortical neurons, ULK4 overexpression inhibited apoptosis, and reduced neurological deficit scores, cerebral infarct volume, and histopathological damage. Moreover, ULK4 overexpression increased PI3K expression and the p-protein kinase B/AKT and p-glycogen synthase kinase 3 beta (GSK3 beta)/GSK3 beta ratios, and inhibited apoptosis, while a PI3K inhibitor reversed the effects of ULK4 overexpression on CIRI. Conclusions ULK4 protects against CIRI, and the underlying mechanism involves PI3K pathway activation which in turn inhibits apoptosis."

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