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Within the Brain: The Renin Angiotensin System.

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TLDR
In this review, the preclinical and clinical evidence for the impact of RAS modulators on cognitive impairment of multiple etiologies will be discussed and the expression and function of different receptor subtypes within the RAS, on different cell types within the brain are presented.
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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Citations
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Targeting Neuroinflammation as a Therapeutic Strategy for Alzheimer's Disease: Mechanisms, Drug Candidates, and New Opportunities

TL;DR: The mechanisms and status of different anti-inflammatory drug candidates for AD that have undergone or are undergoing clinical trials are discussed and new opportunities for targeting neuroinflammation in AD drug development are explored.
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Role of brain renin angiotensin system in neurodegeneration: An update.

TL;DR: The expression of RAS in the brain is discussed and how altered RAS level may cause neurodegeneration is highlighted, suggesting angiotensin II receptor blockers (ARBs) and activation of ACE2/Ang Elliotensin (1–7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenersative diseases.
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Targeting Renin-Angiotensin System Against Alzheimer's Disease

TL;DR: To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.
References
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Journal ArticleDOI

Microglia Promote Learning-Dependent Synapse Formation through Brain-Derived Neurotrophic Factor

TL;DR: It is found that microglia could be specifically depleted from the brain upon diphtheria toxin administration and removal of brain-derived neurotrophic factor (BDNF) frommicroglia largely recapitulated the effects of microglian depletion.
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The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis

TL;DR: White matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting.
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Physiology of local renin-angiotensin systems.

TL;DR: A large body of data is now available to support the existence of numerous organ-based RAS exerting diverse physiological effects, and universal paracrine and autocrine actions may be important in many organ systems and can mediate important physiological stimuli.
Journal ArticleDOI

Continuous c-fos expression precedes programmed cell death in vivo

TL;DR: Evidence is provided showing that the continuous expression of Fos, beginning hours or days before the morphological demise of the cell, appears to be a hallmark of terminal differentiation and a harbinger of death.
Journal ArticleDOI

Inflammation and angiotensin II.

TL;DR: Recent data support the hypothesis that RAS is key mediator of inflammation, and further understanding of the role of the RAS in this process may provide important opportunities for clinical research and treatment of inflammatory diseases.
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