The Brain AT2R—a Potential Target for Therapy in Alzheimer’s Disease and Vascular Cognitive Impairment: a Comprehensive Review of Clinical and Experimental Therapeutics

Ahmed, Heba A.; Ishrat, Tauheed

doi:10.1007/s12035-020-01964-9

Cited by 17 publications

(14 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dementia is most often the result of Alzheimer’s disease (AD), an irreparable, incurable neurodegenerative condition that increases exponentially despite all attempts to overcome it. AD is currently the only leading cause of death that continues to rise, with total costs surpassing cardiovascular disease and cancer combined [ 1 ]. Unfortunately, all the medications currently approved for AD do not reverse or delay the disease’s progressive nature.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, all the medications currently approved for AD do not reverse or delay the disease’s progressive nature. Such agents serve only as palliative measures, their efficacy is reduced over time, and they are often associated with unfavorable side effects [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…All efforts to develop new and more effective treatments for AD have been unsuccessful thus far and have led a large portion of the research community to investigate licensed drugs with potential pharmacological effects applicable to neurodegenerative diseases. This strategy of repurposing existing medications currently approved by the FDA to new therapeutic indications, also referred to as “drug repurposing,” has been successful in many other areas, including cancer and cardiovascular diseases, and effectively minimizes wasted time, effort, resources, and cost [ 1, 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Angiotensin II type 1 receptor (AT1R) blockers (ARBs) are a class of drugs used for the prevention and treatment of cardiovascular disease and have also been shown to protect against cognitive impairment in various clinical and experimental settings [ 1 ]. We and others have shown that the positive effect of ARBs on cognition occurs directly by selectively blocking the AT1R and indirectly, by allowing an unopposed stimulation of the neuroprotective AT2R pathway, by the unbound Ang II [ 1, 5, 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Candesartan is an FDA-approved ARB indicated for the treatment of hypertension in both adults and children and also for heart failure [ 7 ]. It has the strongest AT1R blocking properties of its class [ 8 ] and was selected for our study based on its myriad of advantages, including but not limited to its ability to cross the blood-brain barrier (BBB) [ 9 ] in addition to the extensive data supporting its benefits in cognition [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Candesartan Effectively Preserves Cognition in Senescence Accelerated Mouse Prone 8 (SAMP8) mice

Ahmed

Ishrat

2022

ADR

Self Cite

View full text Add to dashboard Cite

Background: Alzheimer’s disease (AD) has become a worldwide crisis with no effective therapeutic options. The medications currently available for AD are only palliative; their effect is temporary, and they are associated with unfavorable side effects. Even the newest medication aducanumab, granted accelerated FDA approval in 2021, failed to show cognitive benefits in clinical trials and continued approval requires verification in subsequent clinical trials. There is an urgent need for safe and effective therapies to preserve cognition and effectively manage AD. Generally, a new drug product takes several years for FDA approval and exceeds 2.5 billion dollars in research and development, with most new drug products never even reaching the market. This has led to a recent shift for repurposing/repositioning existing FDA-approved medications, to new therapeutic indications. Objective: To investigate the effects of long-term treatment with candesartan, an FDA-approved angiotensin-II type-1 receptor blocker (ARB), on the development of cognitive impairment associated with premature aging. Methods: Candesartan was given at a dose of 1 mg/kg/d in an AD model of senescence-accelerated mouse prone-8 (SAMP8) and senescence-accelerated mouse resistant (SAMR1) mice. Oral treatment with candesartan or vehicle was started, in 2-month-old mice and administered continuously for 4-months. Results: Low-dose candesartan prevents the development of cognitive impairment, otherwise associated with accelerated aging, in SAMP8 mice, because of reduced inflammation and nitro-oxidative stress. SAMR1 animals treated with or without candesartan did not affect the learning and memory of control SAMR1 mice. Conclusion: Early ARB treatment might be beneficial in preventing age-related cognitive deficits in AD-prone individuals.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Candesartan Effectively Preserves Cognition in Senescence Accelerated Mouse Prone 8 (SAMP8) mice

Ahmed

Ishrat

2022

ADR

Self Cite

View full text Add to dashboard Cite

show abstract

Exploring the Mechanism of Arctium Lappa L. Leaves in the Treatment of Alzheimer's Disease Based on Chemical Profile, Network Pharmacology and Molecular Docking

Xue

Qin

et al. 2023

Advanced Biology

View full text Add to dashboard Cite

Alzheimer's Disease (AD) is an irreversible neurodegenerative disease, which urgently needs more effective treatment strategies. Arctium lappa L. leaf (burdock leaf) performs wide pharmacological activities, increasing evidence hinted that burdock leaves can ameliorate AD. This research aims to explore the bioactive ingredients and mechanisms of burdock leaves against AD by performing chemical profiles, network pharmacology, and molecular docking. 61 components are identified by liquid chromatography equipped with mass spectrometry. 792 targets of ingredients and 1661 AD‐related genes are retrieved from public databases. Ten critical ingredients are identified from the topology analysis of the compound‐target network. CytoNCA, AlzData database, and Aging Atlas database contribute to the foundation of 36 potential targets and four clinically significant targets (STAT3, RELA, MAPK8, and AR). The gene ontology (GO) analysis manifests that the included processes are close to the pathogenesis of AD. PI3K‐Akt signaling pathway and AGE‐RAGE signaling pathway may be important therapeutic mechanisms. Molecular docking results imply that network pharmacology results are reliable. Furthermore, the clinical meanings of core targets are also evaluated with the Gene Expression Omnibus (GEO) database. This research will provide research direction for the application of burdock leaves in the treatment of AD.

show abstract

Angiotensin Receptor Blockers and Cognition: a Scoping Review

Zhou,

Orchard,

Nelson

et al. 2023

Curr Hypertens Rep

View full text Add to dashboard Cite

Purpose of Review To provide an overview of the association between angiotensin II receptor blocker (ARB) use and cognitive outcomes. Recent Findings ARBs have previously shown greater neuroprotection compared to other anti-hypertensive classes. The benefits are primarily attributed to the ARB’s effect on modulating the renin-angiotensin system via inhibiting the Ang II/AT1R pathway and activating the Ang II/AT2R, Ang IV/AT4R, and Ang-(1–7)/MasR pathways. These interactions are associated with pleiotropic neurocognitive benefits, including reduced β-amyloid accumulation and abnormal hyperphosphorylation of tau, ameliorated brain hypo-fusion, reduced neuroinflammation and synaptic dysfunction, better neurotoxin clearing, and blood–brain barrier function restoration. While ACEis also inhibit AT1R, they simultaneously lower Ang II and block the Ang II/AT2R and Ang IV/AT4R pathways that counterbalance the potential benefits. Summary ARBs may be considered an adjunctive approach for neuroprotection. This preliminary evidence, coupled with their underlying mechanistic pathways, emphasizes the need for future long-term randomized trials to yield more definitive results.

show abstract

The Brain AT2R—a Potential Target for Therapy in Alzheimer’s Disease and Vascular Cognitive Impairment: a Comprehensive Review of Clinical and Experimental Therapeutics

Cited by 17 publications

References 126 publications

Candesartan Effectively Preserves Cognition in Senescence Accelerated Mouse Prone 8 (SAMP8) mice

Candesartan Effectively Preserves Cognition in Senescence Accelerated Mouse Prone 8 (SAMP8) mice

Exploring the Mechanism of Arctium Lappa L. Leaves in the Treatment of Alzheimer's Disease Based on Chemical Profile, Network Pharmacology and Molecular Docking

Angiotensin Receptor Blockers and Cognition: a Scoping Review

Contact Info

Product

Resources

About