ArticleProceedings of the National Academy of Sciences of the United States of America2016
Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 110 papers.
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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.
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Who cites it
110 citing papers in PubMed, 182 citations in OpenAlex.
- Neuroinflammatory and molecular pathways in Alzheimer's disease: mechanistic crosstalk and emerging therapeutic opportunities.Inflammopharmacology · 2026Review
- Decreased H3K79 acetylation and dysregulation of neurodevelopmental genes in fetal down syndrome.Translational pediatrics · 2026Article
- Calbindin-D28k deficiency mediates tau-driven hippocampal hyperexcitement and cognitive impairment.Translational neurodegeneration · 2026Article
- PMSA as a potential modulator of calcineurin phosphatase activity.Scientific reports · 2026Article
- Exploring the Therapeutic Potential of Piezo1 in Ageing-Related Neurodegenerative Diseases.Journal of molecular neuroscience : MN · 2026Review
- Engram cell vulnerability in neurodegeneration: from mechanistic insights to therapeutic horizons.Frontiers in aging neuroscience · 2026Review
- Role of Mitochondrial Calcium Dysregulation in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2025Review
- Death-associated protein kinase 1-dependent SENP1 degradation increases tau SUMOylation and leads to cognitive dysfunction in a mouse model for tauopathy.Molecular neurodegeneration · 2025Article
- Common Mechanism Underlying Synaptic Dysfunction Caused by Preformed Fibril-Induced Accumulation of α-Synuclein or Tau in a Culture Propagation Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Upregulating ANKHD1 in PS19 Mice Reduces Tau Phosphorylation and Mitigates Tau Toxicity-Induced Cognitive Deficits.International journal of molecular sciences · 2025Article
- Non-mutated human tau stimulates Alzheimer's disease-relevant neurodegeneration in a microglia-dependent manner.Scientific reports · 2025Article
- Understanding the Intersection Between Hormonal Dynamics and Brain Plasticity in Alzheimer's Disease: A Narrative Review for Implementing New Therapeutic Strategies.Health science reports · 2025Review
- Interplay Between Aging and Tau Pathology in Alzheimer's Disease: Mechanisms and Translational Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer's disease.Nature medicine · 2025Article
- Improving vulnerable Calbindin1Translational neurodegeneration · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Hypoxic Postconditioning Offers Neuroprotection Against Transient Cerebral Ischemia via Down-Regulation of rno_piR_011022.CNS neuroscience & therapeutics · 2025Article
- Deciphering T Cell Dynamics in Alzheimer's Disease Pathogenesis: Insights and Implications.Current neuropharmacology · 2025Review
- Paradoxical attenuation of early amyloid-induced cognitive impairment and synaptic plasticity in an aged APP/Tau bigenic rat model.Acta neuropathologica communications · 2024Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Intracellular accumulation of wild-type tau is a hallmark of sporadic Alzheimer's disease (AD), but the molecular mechanisms underlying tau-induced synapse impairment and memory deficit are poorly understood. Here we found that overexpression of human wild-type full-length tau (termed hTau) induced memory deficits with impairments of synaptic plasticity. Both in vivo and in vitro data demonstrated that hTau accumulation caused remarkable dephosphorylation of cAMP response element binding protein (CREB) in the nuclear fraction. Simultaneously, the calcium-dependent protein phosphatase calcineurin (CaN) was up-regulated, whereas the calcium/calmodulin-dependent protein kinase IV (CaMKIV) was suppressed. Further studies revealed that CaN activation could dephosphorylate CREB and CaMKIV, and the effect of CaN on CREB dephosphorylation was independent of CaMKIV inhibition. Finally, inhibition of CaN attenuated the hTau-induced CREB dephosphorylation with improved synapse and memory functions. Together, these data indicate that the hTau accumulation impairs synapse and memory by CaN-mediated suppression of nuclear CaMKIV/CREB signaling. Our findings not only reveal new mechanisms underlying the hTau-induced synaptic toxicity, but also provide potential targets for rescuing tauopathies.
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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.