Involvement of TRPM7 calcium channels and PI3K/AKT kinase pathway in protective effect of vascular endothelial growth factor in amyloid beta-induced model of Alzheimer’s disease

Authors

Abstract

Background and Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, in which cortical and hippocampus neurons death is the main target of neurodegeneration. In addition to extracellular beta amyloid accumulation and the production of neural tangles, one of effective factors in the pathology of Alzheimer's disease is vascular injury in the elderly including disturbance in vascular endothelial growth factor (VEGF) function. The present study was conducted to investigate the effect of pre-treatment with different concentrations of VEGF in a cellular model of Aβ-induced Alzheimer's disease.
 
Materials and Methods: After culturing and passaging human neuroblastoma cells (SH-SY5Y), they were evaluated in control, control pretreated with different concentrations of VEGF (0.5, 1 and 2 nM), amyloid beta, amyloid beta with the same concentrations of VEGF, and amyloid beta pretreated with the most effective concentration of VEGF in addition to TRPM7 channels antagonist (2-APB) or AKT inhibitor. For assessment of cell viability, MTT assay was applied.
 
Results: Findings of this study showed that amyloid beta significantly reduces cell viability (p<0.001), VEGF pretreatment significantly increases cell viability in a concentration-dependent manner, and this beneficial effect was not observed in the presence of TRPM7 channels antagonist or AKT inhibitor.
 
Conclusion: It is concluded that VEGF could prevent amyloid beta-induced reduction of cell viability and its beneficial effect is mediated through TRPM7 channels and PI3K/Akt signaling.
 

Keywords


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