ArticleBiochimica et biophysica acta2016
Calcineurin proteolysis in astrocytes: Implications for impaired synaptic function.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Systematic review of human post-mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease.Neuropathology and applied neurobiology · 2022Pooled it
- A single mild closed-head injury disrupts synaptic strength and promotes hippocampal hyperexcitability in mice.Brain communications · 2026Article
- Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet-Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Inhibition of astrocyte signaling leads to sex-specific changes in microglia phenotypes in a diet-based model of cerebral small vessel disease.Journal of neuroinflammation · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Development of a monoclonal antibody specific for a calpain-generated ∆48 kDa calcineurin fragment, a marker of distressed astrocytes.Journal of neuroscience methods · 2024Article
- Modeling transient ischemic attack via photothrombosis.Biophysical reviews · 2023Review
- Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Targeting Astrocyte Signaling Alleviates Cerebrovascular and Synaptic Function Deficits in a Diet-Based Mouse Model of Small Cerebral Vessel Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Soluble TNF mediates amyloid-independent, diet-induced alterations to immune and neuronal functions in an Alzheimer's disease mouse model.Frontiers in cellular neuroscience · 2023Article
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
- Is It Time to Repurpose Calcineurin Inhibitors for the Treatment of Cognitive Impairment and Dementia?Journal of Alzheimer's disease : JAD · 2023Article
- Why antidiabetic drugs are potentially neuroprotective during the Sars-CoV-2 pandemic: The focus on astroglial UPR and calcium-binding proteins.Frontiers in cellular neuroscience · 2022Review
- Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease.Ageing research reviews · 2021Review
- IGeroScience · 2021Article
- Calmodulin and Its Binding Proteins in Parkinson's Disease.International journal of molecular sciences · 2021Review
- The Astrogenic Balance in the Aging Brain.Current neuropharmacology · 2021Review
- Astrocyte mitochondria: Central players and potential therapeutic targets for neurodegenerative diseases and injury.Ageing research reviews · 2020Article
- Calcineurin-Mediated Hippocampal Inflammatory Alterations in Streptozotocin-Induced Model of Dementia.Molecular neurobiology · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
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Abstract
Mounting evidence suggests that astrocyte activation, found in most forms of neural injury and disease, is linked to the hyperactivation of the protein phosphatase calcineurin. In many tissues and cell types, calcineurin hyperactivity is the direct result of limited proteolysis. However, little is known about the proteolytic status of calcineurin in activated astrocytes. Here, we developed a polyclonal antibody to a high activity calcineurin proteolytic fragment in the 45-48kDa range (ΔCN) for use in immunohistochemical applications. When applied to postmortem human brain sections, the ΔCN antibody intensely labeled cell clusters in close juxtaposition to amyloid deposits and microinfarcts. Many of these cells exhibited clear activated astrocyte morphology. The expression of ΔCN in astrocytes near areas of pathology was further confirmed using confocal microscopy. Multiple NeuN-positive cells, particularly those within microinfarct core regions, also labeled positively for ΔCN. This observation suggests that calcineurin proteolysis can also occur within damaged or dying neurons, as reported in other studies. When a similar ΔCN fragment was selectively expressed in hippocampal astrocytes of intact rats (using adeno-associated virus), we observed a significant reduction in the strength of CA3-CA1 excitatory synapses, indicating that the hyperactivation of astrocytic calcineurin is sufficient for disrupting synaptic function. Together, these results suggest that proteolytic activation of calcineurin in activated astrocytes may be a central mechanism for driving and/or exacerbating neural dysfunction during neurodegenerative disease and injury.
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Registered trials
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