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Brain Res. 2018 Sep 15;1695:65-77. doi: 10.1016/j.brainres.2018.05.024. Epub 2018 May 19.

Elevating Integrin-linked Kinase expression has rescued hippocampal neurogenesis and memory deficits in an AD animal model.

Author information

1
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.
2
Institute of Brain Science and Disease, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266001, People's Republic of China.
3
BGI-Shenzhen, Shenzhen 518083, People's Republic of China.
4
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.
5
Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People's Republic of China. Electronic address: li_yan13@fudan.edu.cn.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; Hippocampus; ILK; Memory; Neurogenesis

PMID:
29787769
DOI:
10.1016/j.brainres.2018.05.024
[Indexed for MEDLINE]

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