ArticleCellular and molecular neurobiology2018
Excessive Glutamate Stimulation Impairs ACE2 Activity Through ADAM17-Mediated Shedding in Cultured Cortical Neurons.
Article in Cellular and molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Review
- Angiotensin-Converting Enzyme 2 Posttranslational Modifications and Implications for Hypertension and SARS-CoV-2: 2023 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension.Cardiovascular research · 2023Article
- Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: Possible implications for SARS-CoV-2 impact on brain development.Reproductive toxicology (Elmsford, N.Y.) · 2022Article
- The atlas of ACE2 expression in fetal and adult human hearts reveals the potential mechanism of heart-injured patients infected with SARS-CoV-2.American journal of physiology. Cell physiology · 2022Article
- AT1 Receptors: Their Actions from Hypertension to Cognitive Impairment.Cardiovascular toxicology · 2022Review
- Structural Plasticity of the Hippocampus in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- ADAM and ADAMTS disintegrin and metalloproteinases as major factors and molecular targets in vascular malfunction and disease.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Involvement of shedding induced by ADAM17 on the nitric oxide pathway in hypertension.Frontiers in molecular biosciences · 2022Review
- Current opinion in neurological manifestations of SARS-CoV-2 infection.Current opinion in toxicology · 2021Review
- Molecular Mechanisms of Proteins - Targets for SARS-CoV-2 (Review).Sovremennye tekhnologii v meditsine · 2021Review
- Diminazen Aceturate Protects Pulmonary Ischemia-Reperfusion Injury via Inhibition of ADAM17-Mediated Angiotensin-Converting Enzyme 2 Shedding.Frontiers in pharmacology · 2021Article
- Activation of Kinin B1R Upregulates ADAM17 and Results in ACE2 Shedding in Neurons.International journal of molecular sciences · 2020Article
- Kinin B1 Receptor Blockade Prevents Angiotensin II-induced Neuroinflammation and Oxidative Stress in Primary Hypothalamic Neurons.Cellular and molecular neurobiology · 2020Article
- COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside.NPJ Parkinson's disease · 2020Review
- Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.Cellular and molecular life sciences : CMLS · 2019Review
- ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models.Neurochemical research · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The excitotoxicity of glutamate plays an important role in the progression of various neurological disorders via participating in inflammation and neuronal damage. In this study, we identified the role of excessive glutamate stimulation in the modulation of angiotensin-converting enzyme type 2 (ACE2), a critical component in the compensatory axis of the renin-angiotensin system (RAS). In primary cultured cortical neurons, high concentration of glutamate (100 µM) significantly reduced the enzymatic activity of ACE2. The elevated activity of ADAM17, a member of the 'A Disintegrin And Metalloprotease' (ADAM) family, was found to contribute to this glutamate-induced ACE2 down-regulation. The decrease of ACE2 activity could be prevented by pre-treatment with antagonists targeting ionotropic glutamate receptors. In addition, the glutamate-induced decrease in ACE2 activity was significantly attenuated when the neurons were co-treated with MitoTEMPOL or blockers that target oxidative stress-mediated signaling pathway. In summary, our study reveals a strong relationship between excessive glutamate stimulation and ADAM17-mediated impairment in ACE2 activity, suggesting a possible cross-talk between glutamate-induced excitotoxicity and dysregulated RAS.
Indexed as
Identifiers
What OpenQuestion holds
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.