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Review
. 2025 Jul 1;16(1):332.
doi: 10.1186/s13287-025-04430-2.

Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease

Jannette Rodríguez-Pallares  1   2 , Lucia A Garcia-Crivaro  3 , Juan A Parga  3   4 , Jose Luis Labandeira-Garcia  3   4
Affiliations
Review

Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease

Jannette Rodríguez-Pallares et al. Stem Cell Res Ther. .

Abstract

Adult neurogenesis is a complex multiphase process involving the formation and integration of new neurons into existing brain circuits. Although it was first described over 50 years ago and numerous factors involved in regulating neurogenic niches have been extensively studied, the underlying molecular mechanisms and interactions involved in controlling adult neurogenesis are still not fully understood. The renin-angiotensin system (RAS) is a well-known hormonal system that controls water and electrolyte balance and blood pressure. In addition to the circulating RAS, a local brain RAS has been described, with a key role in brain homeostasis. A wealth of evidence has emerged showing the involvement of RAS in neurodegeneration and neuroinflammation as well as in proliferation, differentiation, survival, and regeneration processes. Moreover, RAS has a role in cognitive function, behavioral responses, and dementia, which are closely related to neurogenic areas. This review summarizes the current evidence on the role of RAS in regulating adult neurogenic niches. We critically discuss pre-clinical and clinical studies investigating the role of RAS as a potential therapeutic target to modulate neurogenesis in pathological conditions.

Keywords: AT1 receptors; AT2 receptors; Aging; Angiotensin; Cognitive impairment; Hippocampus; Neurodegeneration; Neuroinflammation; Subependymal zone; Subgranular zone.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of cell lineage progression in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and dentate gyrus (DG). Quiescent neural stem cells (qNSC) give rise to activated NSCs (aNSC) (type 1 cells in the DG and type B1 cells in the V-SVZ), which first transit to highly proliferative progenitor cells (type 2 cells in the DG and type C cells in the V-SVZ) and then to neuroblasts (type 3 cells in the DG and type A cells in the V-SVZ), which mature into neurons
Fig. 2
Fig. 2
Effects of renin-angiotensin system (RAS) on adult neurogenesis. Ang: angiotensin; ACE: angiotensin-converting enzyme; ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; AT1R: angiotensin II type 1 receptor; AT2R: angiotensin II type 2 receptor; MasR: Mas receptor; AT4: angiotensin type 4 receptor; DIZE: diminazene aceturate; APA: aminopeptidase A; APN: aminopeptidase N
Fig. 3
Fig. 3
Mechanisms mediating the effects of peripheral and brain renin-angiotensin system (RAS) in adult neurogenesis. Ang: angiotensin; ACE: angiotensin-converting enzyme; ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; AT1R: angiotensin II type 1 receptor; AT2R: angiotensin II type 2 receptor; MasR: Mas receptor; BBB: blood–brain barrier
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