ArticleScientific reports2016
Aβ Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be Prevented by Glutaminase Inhibition Promoting Neuronal Survival.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Exploring the Etiological Links behind Neurodegenerative Diseases: Inflammatory Cytokines and Bioactive Kynurenines.International journal of molecular sciences · 2020Pooled it
- Association Between CDH1 Downregulation and Lymphocyte Cell-Cycle Dysfunction in Alzheimer's Disease and Mild Cognitive Impairment.Cellular and molecular neurobiology · 2026Article
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- Unique tau- and synuclein-dependent metabolic reprogramming in neurons distinct from normal aging.Aging cell · 2024Article
- Deletion of a core APC/C component reveals APC/C function in regulating neuronal USP1 levels and morphology.Frontiers in molecular neuroscience · 2024Article
- Cancer and Alzheimer's Inverse Correlation: an Immunogenetic Analysis.Molecular neurobiology · 2023Review
- Dityrosine cross-linking and its potential roles in Alzheimer's disease.Frontiers in neuroscience · 2023Review
- The Anaphase-Promoting Complex/Cyclosome Is a Cellular Ageing Regulator.International journal of molecular sciences · 2022Review
- Inhibition of Synaptic Glutamate Exocytosis and Prevention of Glutamate Neurotoxicity by Eupatilin fromInternational journal of molecular sciences · 2022Article
- Article
- APC/C-Cdh1-targeted substrates as potential therapies for Alzheimer's disease.Frontiers in pharmacology · 2022Review
- Amyloid-β Induces Cdh1-Mediated Rock2 Stabilization Causing Neurodegeneration.Frontiers in pharmacology · 2022Article
- Epigenomic Profiles of African-AmericanCirculation. Genomic and precision medicine · 2021Article
- Sleep/Wake Behavior and EEG Signatures of the TgF344-AD Rat Model at the Prodromal Stage.International journal of molecular sciences · 2020Article
- Current Evidence on the Protective Effects of Recombinant Human Erythropoietin and Its Molecular Variants against Pathological Hallmarks of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism.Molecules (Basel, Switzerland) · 2020Review
- Glutamine Antagonist JHU-083 Normalizes Aberrant Hippocampal Glutaminase Activity and Improves Cognition in APOE4 Mice.Journal of Alzheimer's disease : JAD · 2020Article
- Targeting PFKFB3 alleviates cerebral ischemia-reperfusion injury in mice.Scientific reports · 2019Article
- Molecular Inverse Comorbidity between Alzheimer's Disease and Lung Cancer: New Insights from Matrix Factorization.International journal of molecular sciences · 2019Article
- Neuroprotective effects of EpoL against oxidative stress induced by soluble oligomers of Aβ peptide.Redox biology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aβ), a peptide related to Alzheimer's disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca(2+) dysregulation, resulting in neuronal apoptosis. Glutaminase inhibition prevents glutamate excitotoxicity and apoptosis in Aβ treated neurons. Furthermore, glutamate also decreases cdh1 and leads to accumulation of glutaminase, suggesting that there may be a positive feedback loop of cdh1 inactivation. We confirmed the main findings in vivo using microinjection of either Aβ or glutamate in the CA1 region of the rat hippocampus. We show here for the first time in vivo that both Aβ and glutamate cause nuclear exclusion of cdh1 and an increase in glutaminase. These results show that maintaining normal APC/C-Cdh1 activity may be a useful target in Alzheimer's disease treatment.
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