ArticleAging cell2011
Proteolysis of calcineurin is increased in human hippocampus during mild cognitive impairment and is stimulated by oligomeric Abeta in primary cell culture.
Article in Aging cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Cyclosporine A Modulates Neuroinflammation-Related Gene Expression Associated with Alzheimer's Disease in SH-SY5Y Neuronal Cell Line: Is Cyclosporine A Beneficial/Detrimental?Biochemical genetics · 2026Article
- 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
- Changes in Astroglial Water Flow in the Pre-amyloid Phase of the STZ Model of AD Dementia.Neurochemical research · 2024Article
- Age-Related Brain Atrophy and the Positive Effects of Behavioral Enrichment in Middle-Aged Beagles.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Development of a monoclonal antibody specific for a calpain-generated ∆48 kDa calcineurin fragment, a marker of distressed astrocytes.Journal of neuroscience methods · 2024Article
- Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease.Neural regeneration research · 2023Article
- Calcineurin Signalling in Astrocytes: From Pathology to Physiology and Control of Neuronal Functions.Neurochemical research · 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
- Is It Time to Repurpose Calcineurin Inhibitors for the Treatment of Cognitive Impairment and Dementia?Journal of Alzheimer's disease : JAD · 2023Article
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
- The Role of Neuroglial Metabotropic Glutamate Receptors in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Reduced Prevalence of Dementia in Patients Prescribed Tacrolimus, Sirolimus, or Cyclosporine.Journal of Alzheimer's disease : JAD · 2023Article
- Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease.Ageing research reviews · 2021Review
- Tacrolimus Protects against Age-Associated Microstructural Changes in the Beagle Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- A Review of Oxidative Stress Products and Related Genes in Early Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2021Review
- Neurogranin stimulates Ca2+/calmodulin-dependent kinase II by suppressing calcineurin activity at specific calcium spike frequencies.PLoS computational biology · 2020Article
- Calcineurin-Mediated Hippocampal Inflammatory Alterations in Streptozotocin-Induced Model of Dementia.Molecular neurobiology · 2020Article
- AD-Related N-Terminal Truncated Tau Is Sufficient to Recapitulate In Vivo the Early Perturbations of Human Neuropathology: Implications for Immunotherapy.Molecular neurobiology · 2018Article
- Calcineurin: directing the damage in Alzheimer disease: An Editorial for 'Neuronal calcineurin transcriptional targets parallel changes observed in Alzheimer disease brain' on page 24.Journal of neurochemistry · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Recent reports demonstrate that the activation and interaction of the protease calpain (CP) and the protein phosphatase calcineurin (CN) are elevated in the late stages of Alzheimer's disease (AD). However, the extent to which CPs and CN interact during earlier stages of disease progression remains unknown. Here, we investigated CP and CN protein levels in cytosolic, nuclear, and membrane fractions prepared from human postmortem hippocampal tissue from aged non-demented subjects, and subjects diagnosed with mild cognitive impairment (MCI). The results revealed a parallel increase in CP I and the 48 kDa CN-Aα (ΔCN-Aα48) proteolytic fragment in cytosolic fractions during MCI. In primary rat hippocampal cultures, CP-dependent proteolysis and activation of CN was stimulated by application of oligomeric Aβ((1-42)) peptides. Deleterious effects of Aβ on neuronal morphology were reduced by blockade of either CP or CN. NMDA-type glutamate receptors, which help regulate cognition and neuronal viability, and are modulated by CPs and CN, were also investigated in human hippocampus. Relative to controls, MCI subjects showed significantly greater proteolytic levels of the NR2B subunit. Within subjects, the extent of NR2B proteolysis was strongly correlated with the generation of ΔCN-Aα48 in the cytosol. A similar proteolytic pattern for NR2B was also observed in primary rat hippocampal cultures treated with oligomeric Aβ and prevented by inhibition of CP or CN. Together, the results demonstrate that the activation and interaction of CPs and CN are increased early in cognitive decline associated with AD and may help drive other pathologic processes during disease progression.
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