Abstract
Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer’s disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD. Angiotensin II (AngII) via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP) mRNA, β-secretase activity, and presenilin expression. Similarly, it was associated with tau phosphorylation, and reactive oxygen species generation. However, these effects are counterbalanced by Ang II mediated AT2 signaling. The protective effect observed with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) could be as the result of inhibition of Ang II signaling. ARBs also offer additional benefit by shifting the effect of Ang II toward AT2 receptor. To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.
Highlights
Renin Angiotensin System (RAS) is a hormonal system that regulates body fluid, electrolyte homostasis, and vascular tone (Yim and Yoo, 2008; Sparks et al, 2014)
The contradiction could be reconciled by the difference in Alzheimer’s disease (AD) animal models used
The brain RAS is reported to be involved in the development and progression of AD through AT1 receptor via increasing the production of amyloid-β, oxidative stress, inflammatory processes, and decreasing release of acetylcholine
Summary
Renin Angiotensin System (RAS) is a hormonal system that regulates body fluid, electrolyte homostasis, and vascular tone (Yim and Yoo, 2008; Sparks et al, 2014). These classical functions of RAS are mediated by angiotensin effector peptides including Ang II, III and 1–7 (Atlas, 2007). In the central nervous system, angiotensinogen is synthesized by astrocytes and subsequently cleaved by renin, angiotensin converting enzyme (ACE) and aminopeptidases or ACE2 and Neprilysin (Bodiga and Bodiga, 2013) Despite some speculations, it is not clearly known where these RAS enzymes are locally synthesized in the brain (McKinley et al, 2003)
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