ArticleMolecular neurobiology2018
Stimulation of ACE2/ANG(1-7)/Mas Axis by Diminazene Ameliorates Alzheimer's Disease in the D-Galactose-Ovariectomized Rat Model: Role of PI3K/Akt Pathway.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 113 citations in OpenAlex.
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- Intersection of COVID-19 and Alzheimer's Disease: Genetic Insights and Neuropathological Consequences.Biochemical genetics · 2026Review
- Investigating the Neuroprotective Effects of Saw Palmetto Fruit Extract Against D-Galactose and Aluminum Chloride Induced Alzheimer's Disease: In Vivo Study.Neurochemical research · 2026Article
- Ginsenoside Rg1 alleviates HG-induced autophagy of retinal microvascular endothelial cells by activating ACE2/Ang1-7/Mas in vitro.Scientific reports · 2025Article
- Propofol exerted the neuroprotective effects by regulating renin-angiotensin system and mitochondria-associated endoplasmic reticulum membrane in the postoperative cognitive dysfunction.BMC anesthesiology · 2025Article
- Telmisartan mitigates behavioral and cytokine level alterations but impairs spatial working memory in a phencyclidine-induced mouse model of schizophrenia.Psychopharmacology · 2025Article
- The dual role of ACE2 in viral infections and neurodegeneration: mechanisms and therapeutic opportunities.Journal of neurovirology · 2025Review
- Mechanisms of angiotensin II to induce depression in diabetes.Diabetology international · 2025Review
- BDNF/proBDNF Interplay in the Mediation of Neuronal Apoptotic Mechanisms in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Ginger Extract Improves Cognitive Dysfunction via Modulation of Gut Microbiota-Derived Short-Chain Fatty Acids in D-Galactose/Ovariectomy-Induced Alzheimer-Like Disease.Molecular neurobiology · 2025Article
- Drugs repurposing in the experimental models of Alzheimer's disease.Inflammopharmacology · 2025Review
- Diminazene Aceturate (DIZE) Ameliorates Hypertension and Induces Anxiolytic- and Antidepressant-like Effects in TGR(mRen2)27.Protein and peptide letters · 2025Article
- Neurotrophic Effects ofInternational journal of molecular sciences · 2024Article
- The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19.International journal of molecular sciences · 2024Review
- Activation of ACE2/Ang-(1-7)/Mas axis improves cognitive dysfunction induced by isoflurane in mice via inhibiting oxidative stress.Journal of anesthesia and translational medicine · 2024Article
- The potential role of brain renin-angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?Journal of cellular and molecular medicine · 2024Review
- Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS.Inflammopharmacology · 2024Article
- Role of brain renin-angiotensin system in depression: A new perspective.CNS neuroscience & therapeutics · 2024Review
- The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling.Translational neuroscience · 2024Article
- Pharmacologic Activation of Angiotensin-Converting Enzyme II Alleviates Diabetic Cardiomyopathy in db/db Mice by Reducing Reactive Oxidative Stress.Diabetes & metabolism journal · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overactivation of angiotensin-converting enzyme/angiotensin 2/angiotensin receptor-1 (ACE/Ang2/AT1) axis provokes amyloid-β-induced apoptosis and neurodegeneration in Alzheimer's disease (AD). Moreover, activation of AT1 impairs the survival pathway phosphoinositide 3-kinase/protein kinase B (PI3K/Akt). Interestingly, the coupling between ACE2/Ang(1-7)/Mas receptor (MasR) axis and PI3K/Akt activation opposes AT1-induced apoptosis. However, the effect of in vivo stimulation of MasR against AD and its correlation to PI3K/Akt is not yet elucidated. Thus, the present study aimed to investigate the relationship between PI3K/Akt pathway and the activation of ACE2/MasR in the AD model of D-galactose-ovariectomized rats. AD features were induced following 8-week injection of D-galactose (150 mg/kg, i.p.) in ovariectomized female rats. The ACE2 activator dimenazine (15 mg/kg, i.p.) was daily administered for 2 months. DIZE administration boosted the hippocampal expression of ACE2 and Mas receptors while suppressing AT1 receptor. Notably, dimenazine enhanced the expression of phosphorylated survival factors (PI3K, Akt, signal transducer, and activator of transcription-3) and neuroplasticity proteins such as cyclic adenosine monophosphate-responsive element-binding protein and brain-derived neurotrophic factor along with nicotinic and glutamatergic receptors. Such effects were accompanied by suppressing phosphorylated tau and glycogen synthase kinase3β along with caspase-3, cytochrome-c, nuclear factor kappa B, tumor necrosis factor alpha, and glial fibrillary acidic protein contents. Dimenazine ameliorated the histopathological damage observed in D-galactose-ovariectomized rats and improved their learning and recognition memory in Morris water maze and novel object recognition tests. In conclusion, dimenazine-induced stimulation of ACE2/Ang(1-7)/Mas axis subdues cognitive deficits in AD most probably through activation of PI3K/Akt pathway.
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