Evaluation Of Angiotensin Receptor Blockers Against Dementia

Abstract

Dementia is a progressive clinical condition marked by a continuous decline in cognitive newlinefunctions such as memory, reasoning, language, and problem-solving, significantly newlineinterfering with daily life. Among its various causes, Alzheimer s disease (AD) is the newlinemost common, accounting for around 60 80% of all dementia cases. AD is a progressive newlineneurodegenerative disorder primarily associated with memory loss and cognitive newlinedysfunction. So, the present study is focussed on AD like pathology in rats. newlinePathologically, AD is marked by and#946;-amyloid plaque accumulation and neurofibrillary newlinetangles of hyperphosphorylated tau protein, leading to neuron loss and brain shrinkage, newlineparticularly in the cerebral cortex and hippocampus. Other contributors include oxidative newlinestress, neuroinflammation, genetic predisposition, and environmental triggers like newlinealuminum toxicity. Despite over a century of research, a cure for AD remains elusive, newlinewith current treatments only providing symptomatic relief and unable to stop disease newlineprogression. newlineThe Renin-Angiotensin System (RAS) has been shown to play a critical role in AD newlinepathogenesis. Though it is debated whether RAS components are produced locally in the newlinebrain or derived from systemic circulation, evidence suggests both sources interact, newlineespecially in areas lacking a blood-brain barrier. Elevated levels of angiotensinogen, newlineACE1, and Ang II have been observed in AD brains, with ACE1 activity correlating newlinewith amyloid accumulation. The RAS acts via two major pathways: the harmful newlineACE1/Ang II/AT1R pathway and the protective ACE2/Ang-(1 7)/Mas receptor axis, newlineboth of which influence memory and cognition. newlineDrug repurposing, or finding new uses for existing medications, has become a valuable newlinestrategy in drug development. This approach saves time and cost by utilizing already newlineestablished safety and pharmacokinetic data. By facilitating faster transition from newlinepreclinical to clinical studies, drug repurposing addresses urgent medical needs more newlineefficiently. RAS inhibitors (RASi), such as ACE inhibitors and