The extended renin-angiotensin system: a promising target for traumatic brain injury therapeutics

Janatpour, Zachary C; Symes, Aviva J.

doi:10.4103/1673-5374.270304

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and water and sodium homeostasis in the circulation (Perez-Lloret et al, 2017;Janatpour and Symes, 2020). Increasing evidence indicates that the brain has a local RAS independent of peripheral organs.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease

Gao

Chen

et al. 2022

Neural Regen Res

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Section: Introductionmentioning

confidence: 99%

Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease

Gao

Chen

et al. 2022

Neural Regen Res

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“…Brain Injury. Traumatic brain injury is a major health problem with unmet therapeutic need (GBD 2016 Traumatic Brain Injury andSpinal Cord Injury Collaborators, 2019), and a number of studies have indicated that novel treatment strategies may be found within the RAS, as previously reviewed (Janatpour and Symes, 2020;Mirzahosseini et al, 2021;Vadhan and Speth, 2021). Included within these are investigations that indicated that activation of AT 2 R is beneficial in traumatic brain injury.…”

Section: E Lungmentioning

confidence: 99%

The Angiotensin AT₂Receptor: From a Binding Site to a Novel Therapeutic Target

et al. 2022

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NF-jB to enter the nucleus and initiate transcription. Collectively, these events lead to reduced synthesis of proinflammatory cytokines and of cyclooxygenase 2 (COX-2), the enzyme that mediates synthesis of proinflammatory prostaglandins.Key Points related to Section III.C on intracellular signaling are:• The intracellular signaling pathways coupled to this atypical GPCR are equally atypical and very different from the canonical GPCR-mediated signaling events.

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“…Stimulation of the angiotensin-II type 1 receptor (AT1R) by angiotensin-II (Ang-II) activates the NADPH-oxidase complex, leading to pro-inflammatory and oxidative stress promoting processes [20][21][22] . These effects are counteracted by the regulatory RAS (rRAS) (namely Ang-(1-7)) signalling through Mas receptor (MasR) and/or angiotensin-II type 2 receptor (AT2R) signalling 23 .…”

Section: Introductionmentioning

confidence: 99%

Renin Angiotensin System as a Potential Treatment Target for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Báron

Skrobot

Palmer

et al. 2022

Journal of Neurotrauma

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Traumatic brain injury (TBI) is a major health concern and leading cause of death and disability in young adults in the UK and worldwide, however, there is a paucity of disease modifying therapies for the treatment of TBI. This review investigates the potential of the reninangiotensin system (RAS) as a treatment pathway for traumatic brain injury (TBI) in adults.Relevant electronic databases were searched on 18 December 2019, updated 16 May 2021. All English language articles with adult human or animal populations investigating RAS drugs as an intervention for TBI or reporting genetic evidence relevant to the RAS and TBI were screened.Eighteen preclinical RCTs (n=2269) and 2 clinical cohort studies (n=771) were included. Metaanalyses of 6 preclinical randomised-controlled trials (n=99) indicated candesartan improved neurological function short-term (<7 days: standardised mean difference (SMD) 0.61, 95% confidence interval (CI) 0.19 -1.03, I2=0%) and long-term (≥7 days: SMD 1.06, 95% CI 0.38; 1.73, I2=0%) post-TBI. Findings were similar for most secondary outcomes. There was a suggestion of benefit from other RAS-targeting drugs, although evidence was limited due to few small studies. There was insufficient evidence to enable strong assessment of these drugs on mortality post-TBI. We conclude that angiotensin-receptor blockers, especially candesartan, show positive outcomes post-TBI in preclinical studies with moderate quality of evidence (GRADE). More research into the effect of regulatory-RAS targeting drugs is needed. Clinical trials of candesartan following TBI are recommended, due to strong and consistent evidence of neuroprotection shown by these preclinical studies.

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The extended renin-angiotensin system: a promising target for traumatic brain injury therapeutics

Cited by 6 publications

References 11 publications

Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease

Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease

The Angiotensin AT₂Receptor: From a Binding Site to a Novel Therapeutic Target

Renin Angiotensin System as a Potential Treatment Target for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

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The extended renin-angiotensin system: a promising target for traumatic brain injury therapeutics

Cited by 6 publications

References 11 publications

Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease

Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease

The Angiotensin AT2Receptor: From a Binding Site to a Novel Therapeutic Target

Renin Angiotensin System as a Potential Treatment Target for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

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The Angiotensin AT₂Receptor: From a Binding Site to a Novel Therapeutic Target