Within the Brain: The Renin Angiotensin System

Jackson, LaDonya; Eldahshan, Wael; Fagan, Susan; Ergul, Adviye

doi:10.3390/ijms19030876

Cited by 336Renin-Angiotensin System StudiesAlzheimer's disease research and treatmentsProtein Hydrolysis and Bioactive Peptides

Within the Brain: The Renin Angiotensin System

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Jackson, LaDonya, Eldahshan, Wael, Fagan, Susan, Ergul, Adviye·2018·International Journal of Molecular Sciences

DOI 10.3390/ijms19030876PMC PMC5877737

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Abstract

For many years, modulators of the renin angiotensin system (RAS) have been trusted by clinicians for the control of essential hypertension. It was recently demonstrated that these modulators have other pleiotropic properties independent of their hypotensive effects, such as enhancement of cognition. Within the brain, different components of the RAS have been extensively studied in the context of neuroprotection and cognition. Interestingly, a crosstalk between the RAS and other systems such as cholinergic, dopaminergic and adrenergic systems have been demonstrated. In this review, the preclinical and clinical evidence for the impact of RAS modulators on cognitive impairment of multiple etiologies will be discussed. In addition, the expression and function of different receptor subtypes within the RAS such as: Angiotensin II type I receptor (AT1R), Angiotensin II type II receptor (AT2R), Angiotensin IV receptor (AT4R), Mas receptor (MasR), and Mas-related-G protein-coupled receptor (MrgD), on different cell types within the brain will be presented. We aim to direct the attention of the scientific community to the plethora of evidence on the importance of the RAS on cognition and to the different disease conditions in which these agents can be beneficial.

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The balance between the pressor and depressor axis of RAAS is implicated in neurodegenerative and psychiatric disorders.
“In fact, the balance between the pressor and depressor axis of RAAS is implicated in neurodegenerative and psychiatric disorders, as carefully reviewed elsewhere [115, 117].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [117]
Inhibition of the pressor axis attenuates cognitive deficits observed in aging, Alzheimer's disease, Parkinson's disease, vascular cognitive impairment and poststroke cognitive impairment.
“In agreement, inhibition of the pressor axis attenuates cognitive deficits observed in aging, Alzheimer’s disease, Parkinson’s disease, vascular cognitive impairment and poststroke cognitive impairment [117].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [117]
Components of the depressor axis correlate to enhanced cognition and cell survival in the brain, orchestrating antioxidant and anti-inflammatory responses.
“Briefly, components of the depressor axis correlate to enhanced cognition and cell survival in the brain, orchestrating antioxidant, and anti-inflammatory responses.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [117]

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Authors: Jackson, L., Eldahshan, W., Fagan, S., & Ergul, A.
Affiliations: University of Georgia (US)
Corresponding author: Ergul, Adviye
ORCID: Jackson, LaDonya
Eldahshan, Wael
Ergul, Adviye
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2018-03-15
Volume: 19
Issue: 3
Pages: 876
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms19030876
PMC: PMC5877737
OpenAlex: W2791138970
Cited by: 336
References: 145
Citations by year: 2026: 18 · 2025: 39 · 2024: 41 · 2023: 54 · 2022: 46 · 2021: 60 · 2020: 39 · 2019: 30 · 2018: 8
FWCI: 6.39
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Veterans Affairs (BX000347, R01NS083559)
NIH (PO1HL128207, R21NS088016)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Hydrolysis and Bioactive Peptides
Keywords: renin-angiotensin system, cognitive impairment, neuroprotection, essential hypertension, angiotensin II type 1 receptor, angiotensin II type 2 receptor, angiotensin IV receptor, Mas receptor, MrgD receptor, cholinergic system, dopaminergic system, adrenergic system, pleiotropy
MeSH terms: Proto-Oncogene Mas, Animals, Brain, Humans, Renin-Angiotensin System, Neurocognitive Disorders, Angiotensin Receptor Antagonists

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Within the Brain: The Renin Angiotensin System

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