The brain renin angiotensin system: a novel precision target for neurofunctional symptom regulation

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 a promising therapeutic target for interventions in neurological and neuropsychiatric disorders, translational progress is hampered by the lack of an integrative mechanistic framework. We here 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 fronto-striatal reward circuits, hippocampal-prefrontal memory networks and fronto-limbic fear networks. We evaluate the transdiagnostic therapeutic potential in neurological and neuropsychiatric disorders (e.g., depression and dementia) and identify translational barriers and conclude with strategic research priorities to facilitate clinical translation.