Targeting the Renin-Angiotensin System (RAS) for Neuropsychiatric Disorders

Authors

Aline Silva de Miranda
Danielle S Macedo
Natalia P Rocha
Antonio L Teixeira

Publication Date

1-1-2024

Journal

Current Neuropharmacology

Abstract

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic targets.

AIMS: We aim to report current experimental and clinical evidence on the role of RAS in physiology and pathophysiology of mood disorders, schizophrenia, AD and related dementias. We also aim to discuss bottlenecks and future perspectives that can foster the development of new related therapeutic strategies.

CONCLUSION: The available evidence supports positive therapeutic effects for neuropsychiatric disorders with the inhibition/antagonism of the ACE/Ang II/AT1 receptor axis or the activation of the ACE2/Ang-(1-7)/Mas receptor axis. Most of this evidence comes from pre-clinical studies and clinical studies lag much behind, hampering a potential translation into clinical practice.

Keywords

Humans, Renin-Angiotensin System, Peptidyl-Dipeptidase A, Kidney, Peptide Fragments, Alzheimer Disease, Central Nervous System, Renin-angiotensin system, brain, angiotensin-converting enzyme, neuropsychiatry, Schizophrenia, mood disorder, Alzheimer’s disease, dementia

Comments

PMID: 36173067