ACE2/angiotensin-(1–7)/mas receptor axis in the central nervous system

The renin–angiotensin system (RAS) is classically conceived as a circulating hormonal system involved in cardiovascular and renal homeostasis. The discovery that RAS components are locally expressed in the brain tissue pointed out to a role for this system in the pathophysiology of neuropsychiatric diseases, including mood disorders and neurodegenerative and cerebrovascular illnesses. The RAS counterregulatory axis composed by the angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)), and Mas receptor mediates, among others, antiinflammatory, antioxidant, and antiapoptotic processes, frequently opposing the classical RAS arm (ACE/Ang II/AT1 receptor) actions. Accumulating evidence has supported protective roles of the ACE2/Ang-(1–7)/Mas receptor axis in the brain. Herein, we will discuss emerging evidence regarding the role of RAS, mainly focusing in the ACE2-Ang-(1–7)-Mas receptor arm, in brain physiology and pathophysiology. We will also report current experimental and clinical evidence in relation to ACE2 stimulation and Mas receptor agonists as potential therapeutic targets for neuropsychiatric diseases.