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Cited by 134Renin-Angiotensin System StudiesNeurological Disease Mechanisms and TreatmentsAdvanced Glycation End Products research

Brain Renin–Angiotensin System at the Intersect of Physical and Cognitive Frailty

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Cosarderelioglu, Caglar, Nidadavolu, Lolita S., George, Claudene J., Oh, Esther S., Bennett, David A., Walston, Jeremy D., Abadir, Peter M.·2020·Frontiers in Neuroscience
DOI 10.3389/fnins.2020.586314PMC PMC7561440
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Abstract

The renin-angiotensin system (RAS) was initially considered to be part of the endocrine system regulating water and electrolyte balance, systemic vascular resistance, blood pressure, and cardiovascular homeostasis. It was later discovered that intracrine and local forms of RAS exist in the brain apart from the endocrine RAS. This brain-specific RAS plays essential roles in brain homeostasis by acting mainly through four angiotensin receptor subtypes; AT1R, AT2R, MasR, and AT4R. These receptors have opposing effects; AT1R promotes vasoconstriction, proliferation, inflammation, and oxidative stress while AT2R and MasR counteract the effects of AT1R. AT4R is critical for dopamine and acetylcholine release and mediates learning and memory consolidation. Consequently, aging-associated dysregulation of the angiotensin receptor subtypes may lead to adverse clinical outcomes such as Alzheimer’s disease and frailty via excessive oxidative stress, neuroinflammation, endothelial dysfunction, microglial polarization, and alterations in neurotransmitter secretion. In this article, we review the brain RAS from this standpoint. After discussing the functions of individual brain RAS components and their intracellular and intracranial locations, we focus on the relationships among brain RAS, aging, frailty, and specific neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and vascular cognitive impairment, through oxidative stress, neuroinflammation, and vascular dysfunction. Finally, we discuss the effects of RAS-modulating drugs on the brain RAS and their use in novel treatment approaches.

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  • For males, no significant GO terms were identified at 25% FDR; the strongest enrichment with nominal P<0.001 involved immune responses to accumulation of amyloid-β in the brain, such as regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell, and other biological processes recently implicated in AD such as response to angiotensin [

    “For males, we did not identify any significant GO terms at 25% FDR; the strongest enrichment with nominal P-value less than 0.001 involved immune responses to the accumulation of amyloid-β (Aβ) in the brain, such as regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell, and other biological processes recently implicated in AD such”

    From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [57]

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  • Sex-specific DNA methylation differences in Alzheimer’s disease pathology

    Zhang, L., Young, J. I., Gomez, L., Silva, T. C., Schmidt, M. A., Cai, J., Chen, X., Martin, E. R., & Wang, L. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01177-8 · Cited by 58 · see citing works

    “001 involved immune responses to the accumulation of amyloid-β (Aβ) in the brain, such as regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell, and other biological processes recently implicated in AD such as response to angiotensin [57, 58] and cell…”
    Background

Authors
Cosarderelioglu, C., Nidadavolu, L. S., George, C. J., Oh, E. S., Bennett, D. A., Walston, J. D., & Abadir, P. M.
Affiliations
  • Johns Hopkins University (US)
  • Albert Einstein College of Medicine (US)
  • Rush University Medical Center (US)
Corresponding author
Abadir, Peter M.
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2020-09-30
Volume
14
Pages
586314-586314
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2020.586314
PMC
PMC7561440
OpenAlex
W3091639901
Cited by
134
References
30
Citations by year
2026: 14 · 2025: 14 · 2024: 27 · 2023: 30 · 2022: 32 · 2021: 16 · 2020: 1
FWCI
3.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (R01AG046441, R01AG17917)
  • BrightFocus Foundation
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Keywords
brain renin-angiotensin system, physical frailty, cognitive frailty, angiotensin II type 1 receptor, angiotensin II type 2 receptor, Mas receptor, AT4 receptor, aging, Alzheimer's disease, Parkinson's disease, vascular cognitive impairment, oxidative stress, neuroinflammation, endothelial dysfunction, microglial polarization, learning and memory

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