Xu Xu-Feng, Wang You-Cui, Zong Liang, Chen Zhe-Yu, Li Yan
Institute of Brain Science and Disease, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266001, People's Republic of China; Department of Cell and Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science, School of Basic Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.
Institute of Brain Science and Disease, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266001, People's Republic of China.
Brain Res. 2018 Sep 15;1695:65-77. doi: 10.1016/j.brainres.2018.05.024. Epub 2018 May 19.
Alterations in adult neurogenesis have been regarded as a major cause of cognitive impairment in Alzheimer's disease (AD). The underlying mechanism of neurogenesis deficiency in AD remains unclear. In this study, we reported that Integrin-linked Kinase (ILK) protein levels and phosphorylation were significantly decreased in the hippocampus of APP/PS1 mice. Increased ILK expression of dentate gyrus (DG) rescued the hippocampus-dependent neurogenesis and memory deficits in APP/PS1 mice. Moreover, we demonstrated that the effect of ILK overexpression in the hippocampus was exerted via AKT-GSK3β pathway. Finally, we found that Fluoxetine, a selective serotonin reuptake inhibitor, could improve the impaired hippocampal neurogenesis and memory by enhancing ILK-AKT-GSK3β pathway activity in APP/PS1 mice. Thus, these findings demonstrated the effects of ILK on neurogenesis and memory recovery, suggesting that ILK is an important therapeutic target for AD prevention and treatment.
成年神经发生的改变被认为是阿尔茨海默病（AD）认知障碍的主要原因。AD中神经发生缺陷的潜在机制仍不清楚。在本研究中，我们报道APP/PS1小鼠海马中整合素连接激酶（ILK）蛋白水平和磷酸化显著降低。齿状回（DG）中ILK表达的增加挽救了APP/PS1小鼠海马依赖性神经发生和记忆缺陷。此外，我们证明海马中ILK过表达的作用是通过AKT-GSK3β途径发挥的。最后，我们发现选择性5-羟色胺再摄取抑制剂氟西汀可通过增强APP/PS1小鼠的ILK-AKT-GSK3β途径活性来改善受损的海马神经发生和记忆。因此，这些发现证明了ILK对神经发生和记忆恢复的作用，表明ILK是AD预防和治疗的重要治疗靶点。
