Olmesartan Prevents Oligomerized Amyloid β (Aβ)-Induced Cellular Senescence in Neuronal Cells

Alzheimer's disease (AD) is a neurodegenerative disease with high morbidity. The deposition of oligomerized amyloid beta (A beta) is the pathological feature of AD. The A beta-caused neuronal oxidative stress and cellular senescence play an important role in the development and progression of AD. Olmesartan is a novel angiotensin receptor blocker with promising antihypertensive properties and has recently been reported to exert anti-inflammatory and antioxidative stress effects. Blood pressure control using Angiotensin receptor blockers has shown multiple benefits in Alzheimer's disease models. In the present study, the effect of Olmesartan on oligomerized amyloid beta (A beta)-induced cellular senescence was investigated in cultured M17 neuronal cells. Our results show that Olmesartan treatment significantly ameliorates oligomerized A beta-elevated ROS and MDA levels, as well as the induced senescent cells number. At the molecular level, Olmesartan inhibits the elevated expression of senescence biomarkers (p16 and p21). Furthermore, Olmesartan potently reversed the increased K382 acetylation of p53 and the downregulation of SIRT1. Moreover, we show that the effect of Olmesartan against cell senescence and deacetylation of p53 was abolished by inhibition of SIRT1, either by using nicotinamide or by transfection with SIRT1 siRNA. In conclusion, Olmesartan prevents oligomerized A beta-induced cellular senescence in neuronal cells by downregulating p16 and p21 through a SIRT1 dependent deacetylation of p53; our finding indicates that Olmesartan has a protective effect in A beta-induced neurotoxicity.