ArticleBioMed research international2015
Inhibition of ACE Retards Tau Hyperphosphorylation and Signs of Neuronal Degeneration in Aged Rats Subjected to Chronic Mild Stress.
Article in BioMed research international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Renin-angiotensin system gene expression and neurodegenerative diseases.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016Pooled it
- Review
- Associations among Angiotensin-Converting Enzyme, Neuroinflammation, and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in Non-Dementia Adults.Neurotoxicity research · 2025Article
- Associations of renin-angiotensin system inhibitor use with brain insulin signaling and neuropathology.Annals of clinical and translational neurology · 2024Article
- Preclinical Evidence for the Role of the Yin/Yang Angiotensin System Components in Autism Spectrum Disorder: A Therapeutic Target of Astaxanthin.Biomedicines · 2023Article
- Life Experience Matters: Enrichment and Stress Can Influence the Likelihood of Developing Alzheimer's Disease via Gut Microbiome.Biomedicines · 2023Review
- Angiotensin II Increases Oxidative Stress and Inflammation in Female, But Not Male, Endothelial Cells.Cellular and molecular bioengineering · 2023Article
- Article
- Captopril alleviates epilepsy and cognitive impairment by attenuation of C3-mediated inflammation and synaptic phagocytosis.Journal of neuroinflammation · 2022Article
- Involvement of the Renin-Angiotensin System in Stress: State of the Art and Research Perspectives.Current neuropharmacology · 2022Review
- Pharmaceutical Potential of Casein-Derived Tripeptide Met-Lys-Pro: Improvement in Cognitive Impairments and Suppression of Inflammation in APP/PS1 Mice.Journal of Alzheimer's disease : JAD · 2022Article
- Article
- Drug repositioning and repurposing for Alzheimer disease.Nature reviews. Neurology · 2020Review
- Perindopril ameliorates experimental Alzheimer's disease progression: role of amyloid β degradation, central estrogen receptor and hyperlipidemic-lipid raft signaling.Inflammopharmacology · 2020Article
- Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Stress and Alzheimer's disease: A senescence link?Neuroscience and biobehavioral reviews · 2020Review
- Discovery of Pathologic GPCR Aggregation.Frontiers in medicine · 2019Review
- Tauopathy and neurodegeneration: A role for stress.Neurobiology of stress · 2018Review
- Microglial Activation Is Modulated by Captopril:Frontiers in cellular neuroscience · 2018Article
- Targeting Renin-Angiotensin System Against Alzheimer's Disease.Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With increasing life expectancy, Alzheimer's disease (AD) and other types of age-associated dementia are on the rise worldwide. Treatment approaches for dementia are insufficient and novel therapies are not readily available. In this context repurposing of established drugs appears attractive. A well-established class of cardiovascular drugs, which targets the angiotensin II system, is such a candidate, which currently undergoes a paradigm shift with regard to the potential benefit for treatment of neurodegenerative symptoms. In search for additional evidence, we subjected aged rats to chronic unpredictable mild stress, which is known to enhance the development of AD-related neuropathological features. We report here that four weeks of chronic mild stress induced a strong upregulation of the hippocampal angiotensin-converting enzyme (Ace) at gene expression and protein level. Concomitantly, tau protein hyperphosphorylation developed. Signs of neurodegeneration were detected by the significant downregulation of neuronal structure proteins such as microtubule-associated protein 2 (Map2) and synuclein-gamma (Sncg). Ace was involved in neurodegenerative symptoms because treatment with the brain-penetrating ACE inhibitor, captopril, retarded tau hyperphosphorylation and signs of neurodegeneration. Moreover, ACE inhibitor treatment could counteract glutamate neurotoxicity by preventing the downregulation of glutamate decarboxylase 2 (Gad2). Taken together, ACE inhibition targets neurodegeneration triggered by environmental stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.