Potential molecular pathways of angiotensin receptor blockers in the brain toward cognitive improvement in dementia

Abstract

The alarming rise of cognitive impairment and memory decline and limited effective solutions present a worldwide concern for dementia patients. The multivariant role of the renin-angiotensin system (RAS) in the brain offers strong evidence of a role for angiotensin receptor blockers (ARBs) in the management of memory impairment by modifying glutamate excitotoxicity, downregulating inflammatory cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)α, inhibiting kynurenine aminotransferase (KAT)-II, nucleotide-binding domain, leucine-rich-containing family and pyrin-domain-containing-3 (NLRP3) inflammasomes, boosting cholinergic activity, activating peroxisome proliferator-activated receptor (PPAR)-γ, countering cyclooxygenase (COX) and mitigating the hypoxic condition. The present work focuses on the intricate molecular mechanisms involved in brain-RAS, highlighting the role of ARBs, connecting links between evidence-based unexplored pathways and investigating probable biomarkers involved in dementia through supported preclinical and clinical literature.

Keywords: angiotensin-receptor blockers; dementia; molecular mechanisms; neuroprotection; renin–angiotensin system.