Angiotensin-converting enzymes as druggable features of psychiatric and neurodegenerative disorders

J Neurochem. 2023 Jul;166(2):138-155. doi: 10.1111/jnc.15806. Epub 2023 Mar 27.

Abstract

The renin-angiotensin system (RAS) plays essential roles in maintaining peripheral cardiovascular homeostasis, with its potential roles in the brain only being recognized more recently. Angiotensin-I-converting enzyme (ACE) is the main component of the RAS, and it has been implicated in various disorders of the brain. ACE and other RAS components, including the related enzyme ACE2, angiotensin peptides and their respective receptors, can participate in the pathological state, as well as with potential to contribute to neuroprotection and/or to complement existing treatments for psychiatric illness. In this narrative review, we aimed to identify the main studies describing the functions of the RAS and ACEs in the brain and their association with brain disorders. These include neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, psychiatric illnesses such as schizophrenia, bipolar disorder, and depression. We also discuss the possible association of a functional polymorphism of the ACE gene with these brain diseases and the relevance of the neuroprotective and anti-inflammatory properties of ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs). Based on this, we conclude that there is significant potential value to the inclusion of ACEis and/or ARBs as a novel integrated approach for the treatment of various disorders of the brain, and particularly for psychiatric illness.

Keywords: ACE inhibitors; angiotensin; angiotensin receptor blocker; angiotensin-I-converting enzyme; brain disorders; renin-angiotensin system.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease*
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors* / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
  • Angiotensins
  • Humans
  • Renin-Angiotensin System

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Angiotensins