angiotensin-i and Brain-Diseases

Angiotensin-converting enzyme 2 (ACE2) is a protein consisting of two domains, the N-terminus is a carboxypeptidase homologous to ACE and the C-terminus is homologous to collectrin and responsible for the trafficking of the neutral amino acid transporter B(0)AT1 to the plasma membrane of gut epithelial cells. The carboxypeptidase domain not only metabolizes angiotensin II to angiotensin-(1-7), but also other peptide substrates, such as apelin, kinins and morphins. In addition, the collectrin domain regulates the levels of some amino acids in the blood, in particular of tryptophan. Therefore it is of no surprise that animals with genetic alterations in the expression of ACE2 develop a diverse pattern of phenotypes ranging from hypertension, metabolic and behavioural dysfunctions, to impairments in serotonin synthesis and neurogenesis. This review summarizes the phenotypes of such animals with a particular focus on the central nervous system.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Animals, Genetically Modified; Brain; Brain Diseases; Cardiomegaly; Models, Animal; Peptide Fragments; Peptidyl-Dipeptidase A; Phenotype; Serotonin; Stress, Psychological; Tryptophan

All the components of the classic renin-angiotensin system (RAS) have been identified in the brain. Today, the RAS is considered to be composed mainly of two axes: the pressor axis, represented by angiotensin (Ang) II/angiotensin-converting enzyme/AT1 receptors, and the depressor and protective one, represented by Ang-(1-7)/ angiotensin-converting enzyme 2/Mas receptors. Although the RAS exerts a pivotal role on electrolyte homeostasis and blood pressure regulation, their components are also implicated in higher brain functions, including cognition, memory, anxiety and depression, and several neurological disorders. Overactivity of the pressor axis of the RAS has been implicated in stroke and several brain disorders, such as cognitive impairment, dementia, and Alzheimer or Parkinson's disease. The present review is focused on the role of the protective axis of the RAS in brain disorders beyond its effects on blood pressure regulation. Furthermore, the use of drugs targeting centrally RAS and its beneficial effects on brain disorders are also discussed.

Topics: Alzheimer Disease; Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Anxiety; Brain Diseases; Cognition; Humans; Peptide Fragments; Renin-Angiotensin System; Stroke; Translational Research, Biomedical