Renin-angiotensin system: a novel target for brain health

Emerging evidence highlights the brain renin-angiotensin system (RAS) as a key regulator of reward, memory, and stress. While these discoveries established the brain RAS as a promising therapeutic target for interventions in neurological and neuropsychiatric disorders, translational progress is hampered by the lack of an integrative mechanistic framework. Here, we consolidate accumulating evidence on the molecular and system-level roles of the brain RAS in reward, memory, and stress pathways, and its dual regulatory architecture. Pharmacological RAS modulation regulates domain-specific signaling in frontostriatal reward circuits, hippocampal-prefrontal memory networks, and frontolimbic fear networks. We evaluate the transdiagnostic therapeutic potential in neurological and neuropsychiatric disorders (e.g., dementia and depression), identify translational barriers, and conclude with strategic research priorities to facilitate clinical translation.