Potential molecular pathways of angiotensin receptor blockers in the brain toward cognitive improvement in dementia
DRUG DISCOVERY TODAY(2024)
摘要
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)-1b, IL-6 and tumor necrosis factor (TNF)a, inhibiting kynurenine aminotransferase (KAT)-II, nucleotide-binding domain, leucine-rich-containing family and pyrin-domain-containing-3 (NLRP3) inflam-masomes, boosting cholinergic activity, activating peroxisome proliferator-activated receptor (PPAR)-c, 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.
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关键词
dementia,angiotensin-receptor blockers,renin-angiotensin system,molecular mechanisms,neuroprotection
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