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

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.

Keywords: Alzheimer’s disease; Hippocampus; ILK; Memory; Neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cognitive Dysfunction / metabolism
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Memory / physiology
  • Memory Disorders / metabolism*
  • Mice, Transgenic
  • Neurogenesis / physiology*
  • Protein-Serine-Threonine Kinases / metabolism*


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • integrin-linked kinase
  • Protein-Serine-Threonine Kinases