Beneficial effects of Angiotensin II receptor blockers in brain disorders

Abstract

A canonical brain Renin-Angiotensin System (RAS), like the canonical peripheral RAS, has long been proposed as a major regulator of brain function. Because of methodological limitations, however, this system is in urgent need of critical revision. The Angiotensin II AT1 receptors have been confirmed as key factors in the regulation of brain function, and AT1 receptor over activity has been established as a major and early injury factor in the development of many brain diseases. Consequently, Angiotensin Receptor Blockers (ARBs), compounds widely used to treat cardiovascular and metabolic disorders, are excellent candidates for repurposing for the treatment of brain disorders. This review will discuss some of the reasons why revisiting brain RAS is a pressing necessity, will present evidence for a participation of AT1 receptor over activity in the development of major brain disorders, and will present definite evidence of ARBs neuroprotective effects. The review will focus on the beneficial effects of ARB therapy in stroke, neurodegenerative disorders including Alzheimer's and Parkinson's diseases, traumatic brain injury, radiation- induced brain damage, stress and mood disorders.

Keywords: Angiotensin receptor blockers; Brain Renin Angiotensin System; Neurodegenerative disorders; Neuroprotection; Traumatic and radiation brain injury.