Differential effects of angiotensin II receptor blockers on Aβ generation

NEUROSCIENCE LETTERS

卷:567

Article

Liu, Junjun¹  Liu, Shuyu¹  Tanabe, Chiaki¹  Maeda, Tomoji¹  Zou, Kun¹  Komano, Hiroto¹ 

[1] Iwate Med Univ, Sch Pharm, Dept Neurosci, Yahaba, Iwate 0283694, Japan

关键词: Alzheimer's disease;    Amyloid beta-protein;    Angiotensin II receptor blockers;   

DOI  :  10.1016/j.neulet.2014.03.030

来源: Elsevier

【 摘 要 】

Angiotensin II receptor blockers (ARBs) are widely prescribed for the medication of systemic hypertension and congestive heart failure. It has been reported that ARBs can reduce the risk for the onset of Alzheimer's disease (AD) and have beneficial effects on dementia. Neurotoxic amyloid beta-protein (A beta) is believed to play a causative role in the development of AD. However, whether ARBs regulate A beta generation remains largely unknown. Here, we studied the effect of ARBs on A beta generation and found that telmisartan significantly increased A beta 40 and A beta 42 generation, but decreased the A beta 42/A beta 40 ratio. However, losartan, valsartan and candesartan did not increase A beta generation, while olmesartan significantly increased A beta 42 generation. We also found that telmisartan increased the A beta generation through angiotensin type 1 a receptor (AT1a) and the receptor-related phosphotidylinositide 3-kinases (PI3K) pathway. Our findings revealed the different effects of ARBs on A beta generation and provide new evidence for the relationship between antihypertensive treatment and AD pathogenesis. 2014 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free