The effects of the renin inhibitor aliskiren on neuronal toxic damage.

The neurotoxicity of amyloid-β (Aβ) and its deposition in neurons plays a critical role in the occurrence and development of Alzheimer's disease (AD). Several preclinical experiments have found that the renin inhibitor aliskiren has a wide range of physiological effects, including hindering the progression of atherosclerosis and anti-inflammatory. This study is aimed to explore the effect of aliskiren on neuronal toxic damage and the underlying mechanism. This study established an nerve injury model through Aβ induction; the effects of aliskiren on the viability, inflammatory damage and apoptosis of SH-SY5Y cells were examined. For the sake of explore the underlying mechanism; SwissTargetPrediction website and molecular docking were utilized to predict the target of aliskiren. Then the impacts of the target protein overexpression were determined to verify its mediation. The results of the current study demonstrate that aliskiren has no effect on the viability of SH-SY5Y cells while Aβaccumulation could significantly downregulate cell viability. In addition, aliskiren could alleviate neuronal inflammatory damage and apoptosis arise from Aβ accumulation. Following confirming the high expression level of the predicted target PDE4B in damaged cells, it was found that PDE4B overexpression can reverse the influence of aliskiren on cell viability, inflammatory damage and apoptosis. In conclusion, aliskiren upregulates cell viability, reduces inflammatory damage and apoptosis induced by Aβ accumulation in AD inhibiting PDE4B. These findings have expanded the scope of future application of aliskiren and provided a theoretical basis.