ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin/NFAT signaling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 5 of them syntheses that pooled it.
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Who cites it
188 citing papers in PubMed, 5 syntheses or guidelines pooled it, 332 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
- EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review.Frontiers in neuroscience · 2022Pooled it
- Meta-analysis of mouse transcriptomic studies supports a context-dependent astrocyte reaction in acute CNS injury versus neurodegeneration.Journal of neuroinflammation · 2020Pooled it
- The neuropathological profile of mild cognitive impairment (MCI): a systematic review.Molecular psychiatry · 2012Pooled it
- Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment.Current Alzheimer research · 2018Trial
- Differential DNA methylation in blood as potential mediator of the association between ambient PMMolecular psychiatry · 2026Article
- Single-cell multiomics connects 3D genome and transcriptome alterations in Alzheimer's disease.Science (New York, N.Y.) · 2026Article
- 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
- Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.Nature reviews. Neuroscience · 2026Review
- Evaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin.Molecular neurobiology · 2025Article
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- 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
- Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy.Brain sciences · 2025Article
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- AI-Powered Mice Behavior Tracking and Its Application for Neuronal Manifold Analysis Based on Hippocampal Ensemble Activity in an Alzheimer's Disease Mice Model.International journal of molecular sciences · 2025Article
- A Positive Allosteric Modulator of the SERCA Pump Rescues Hippocampal Neuronal Circuits Dysfunction and Cognitive Defects in a Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Soluble β-Amyloid Oligomers Selectively Upregulate TRPC3 in Excitatory Neurons via Calcineurin-Coupled NFAT.Cells · 2025Article
- Target the Heart: A New Axis of Alzheimer's Disease Prevention.Journal of dementia and alzheimer's disease · 2025Article
- Celebrating 40 years of the University of Kentucky Alzheimer's Disease Research Center.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
128 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Upon activation by calcineurin, the nuclear factor of activated T-cells (NFAT) translocates to the nucleus and guides the transcription of numerous molecules involved in inflammation and Ca(2+) dysregulation, both of which are prominent features of Alzheimer's disease (AD). However, NFAT signaling in AD remains relatively uninvestigated. Using isolated cytosolic and nuclear fractions prepared from rapid-autopsy postmortem human brain tissue, we show that NFATs 1 and 3 shifted to nuclear compartments in the hippocampus at different stages of neuropathology and cognitive decline, whereas NFAT2 remained unchanged. NFAT1 exhibited greater association with isolated nuclear fractions in subjects with mild cognitive impairment (MCI), whereas NFAT3 showed a strong nuclear bias in subjects with severe dementia and AD. Similar to NFAT1, calcineurin-Aalpha also exhibited a nuclear bias in the early stages of cognitive decline. But, unlike NFAT1 and similar to NFAT3, the nuclear bias for calcineurin became more pronounced as cognition worsened. Changes in calcineurin/NFAT3 were directly correlated to soluble amyloid-beta (Abeta((1-42))) levels in postmortem hippocampus, and oligomeric Abeta, in particular, robustly stimulated NFAT activation in primary rat astrocyte cultures. Oligomeric Abeta also caused a significant reduction in excitatory amino acid transporter 2 (EAAT2) protein levels in astrocyte cultures, which was blocked by NFAT inhibition. Moreover, inhibition of astrocytic NFAT activity in mixed cultures ameliorated Abeta-dependent elevations in glutamate and neuronal death. The results suggest that NFAT signaling is selectively altered in AD and may play an important role in driving Abeta-mediated neurodegeneration.
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Registered trials
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