ArticleJournal of neurochemistry2011
Dysregulated phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II-α in the hippocampus of subjects with mild cognitive impairment and Alzheimer's disease.
Article in Journal of neurochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- A meta-analysis of gene expression data highlights synaptic dysfunction in the hippocampus of brains with Alzheimer's disease.Scientific reports · 2020Pooled it
- mTORC2-NaChannels (Austin, Tex.) · 2026Article
- The Janus face of CaMKII: from memory consolidation to neurotoxic switch in Alzheimer's disease.Archives of toxicology · 2025Review
- AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.Translational neurodegeneration · 2025Review
- Role of Oxidative Stress, Methionine Oxidation and Methionine Sulfoxide Reductases (MSR) in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- DeepGAMI: deep biologically guided auxiliary learning for multimodal integration and imputation to improve genotype-phenotype prediction.Genome medicine · 2023Article
- Alzheimer's Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression.Current issues in molecular biology · 2023Review
- Pin1 and Alzheimer's disease.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Phenylethanoid Glycosides of Cistanche Improve Learning and Memory Disorders in APP/PS1 Mice by Regulating Glial Cell Activation and Inhibiting TLR4/NF-κB Signaling Pathway.Neuromolecular medicine · 2023Article
- The Effects of Ninjinyoeito on Impaired Spatial Memory and Prefrontal Cortical Synaptic Plasticity throughEvidence-based complementary and alternative medicine : eCAM · 2023Article
- Neuroprotective effect of dexmedetomidine on autophagy in mice administered intracerebroventricular injections of AβFrontiers in pharmacology · 2023Article
- Article
- CaMKIIα Signaling Is Required for the Neuroprotective Effects of Dl-3-n-Butylphthalide in Alzheimer's Disease.Molecular neurobiology · 2022Article
- Tranilast, a Transient Receptor Potential Vanilloid 2 Channel (TRPV2) Inhibitor Attenuates Amyloid β-Induced Cognitive Impairment: Possible Mechanisms.Neuromolecular medicine · 2022Article
- Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q.Science translational medicine · 2022Article
- Neuroprotective Effect of 2-Aminoethoxydiphenyl Borate (2-APB) in Amyloid β-Induced Memory Dysfunction: A Mechanistic Study.Cellular and molecular neurobiology · 2022Article
- Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APPInternational journal of molecular sciences · 2022Article
- Emerging insights into synapse dysregulation in Alzheimer's disease.Brain communications · 2022Review
- Novel Biomarkers of Alzheimer's Disease: Based Upon N-methyl-D-aspartate Receptor Hypoactivation and Oxidative Stress.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2021Review
- Calbindin regulates Kv4.1 trafficking and excitability in dentate granule cells via CaMKII-dependent phosphorylation.Experimental & molecular medicine · 2021Article
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4 authors at 2 institutions in 1 country.
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Abstract
Alzheimer's disease (AD) is a progressive, neurodegenerative disorder and the most prevalent senile dementia. The early symptom of memory dysfunction involves synaptic loss, thought to be mediated by soluble amyloid-beta (Aβ) oligomers. These aggregate species target excitatory synapses and their levels correlate with disease severity. Studies in cell culture and rodents have shown that oligomers increase intracellular calcium (Ca(2+)), impairing synaptic plasticity. Yet, the molecular mechanism mediating Aβ oligomers' toxicity in the aged brain remains unclear. Here, we apply quantitative immunofluorescence in human brain tissue from clinically diagnosed mild cognitive impaired (MCI) and AD patients to investigate the distribution of phosphorylated (active) Ca(2+) /calmodulin-dependent protein kinase-α (p(Thr286)CaMKII), a critical enzyme for activity-dependent synaptic remodeling associated with cognitive function. We show that p(Thr286)CaMKII immunoreactivity is redistributed from dendritic arborizations to neural perikarya of both MCI and AD hippocampi. This finding correlates with cognitive assessment scores, suggesting that it may be a molecular read-out of the functional deficits in early AD. Treatment with oligomeric Aβ replicated the observed phenotype in mice and resulted in a loss of p(Thr286)CaMKII from synaptic spines of primary hippocampal neurons. Both outcomes were prevented by inhibiting the phosphatase calcineurin (CaN). Collectively, our results support a model in which the synaptotoxicity of Aβ oligomers in human brain involves the CaN-dependent subcellular redistribution of p(Thr286)CaMKII. Therapies designed to normalize the homeostatic imbalance of neuronal phosphatases and downstream dephosphorylation of synaptic p(Thr286)CaMKII should be considered to prevent and treat early AD.
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Registered trials
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.