ArticleNeurobiology of aging2015
Intraneuronal Aβ accumulation induces hippocampal neuron hyperexcitability through A-type K(+) current inhibition mediated by activation of caspases and GSK-3.
Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07732933 (GSK-3 as a Target for Lithium-charged Au Nanoparticles in Bipolar Disorder), which is not on this map. Cited by 68 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
GSK-3 as a Target for Lithium-charged Au Nanoparticles in Bipolar Disorder
Who cites it
68 citing papers in PubMed, 98 citations in OpenAlex.
- Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model.Nature communications · 2026Article
- Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis.Nature aging · 2026Article
- Therapeutic Options for Alzheimer's Disease and Aging-Associated Cognitive Decline: State of the Art in the ACH2.0 Paradigm.International journal of molecular sciences · 2026Review
- Disorganized hippocampal excitatory and inhibitory connectivity in a mouse model of Alzheimer's disease.IBRO neuroscience reports · 2025Article
- Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERRα dysregulation and energy dyshomeostasis.Nature communications · 2025Article
- Amyloid β-dependent neuronal silencing through synaptic decoupling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Alzheimer's Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory.International journal of molecular sciences · 2025Review
- Gene Expression Signatures of Immaturity, Decreased pH, and Neural Hyperexcitation in the Hippocampus of Alzheimer's Disease Model Mice.Neuropsychopharmacology reports · 2025Article
- Article
- Structural and functional alterations of neurons derived from sporadic Alzheimer's disease hiPSCs are associated with downregulation of the LIMK1-cofilin axis.Alzheimer's research & therapy · 2024Article
- Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Chronic rapid eye movement sleep deprivation aggravates the pathogenesis of Alzheimer's disease by decreasing brain O-GlcNAc cycling in mice.Journal of neuroinflammation · 2024Article
- ACH2.0/E, the Consolidated Theory of Conventional and Unconventional Alzheimer's Disease: Origins, Progression, and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- On the Inadequacy of the Current Transgenic Animal Models of Alzheimer's Disease: The Path Forward.International journal of molecular sciences · 2024Article
- Neuroprotective Effects of Ferrostatin and Necrostatin Against Entorhinal Amyloidopathy-Induced Electrophysiological Alterations Mediated by voltage-gated CaNeurochemical research · 2024Article
- Next Generation Therapeutic Strategy for Treatment and Prevention of Alzheimer's Disease and Aging-Associated Cognitive Decline: Transient, Once-in-a-Lifetime-Only Depletion of Intraneuronal Aβ (International journal of molecular sciences · 2023Article
- Amyloid-β Effects on Peripheral Nerve: A New Model System.International journal of molecular sciences · 2023Article
- Characterization of age- and stage-dependent impaired adult subventricular neurogenesis in 5XFAD mouse model of Alzheimer's disease.BMB reports · 2023Article
- The Amyloid Cascade Hypothesis 2.0 for Alzheimer's Disease and Aging-Associated Cognitive Decline: From Molecular Basis to Effective Therapy.International journal of molecular sciences · 2023Article
8 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Amyloid β-protein (Aβ) pathologies have been linked to dysfunction of excitability in neurons of the hippocampal circuit, but the molecular mechanisms underlying this process are still poorly understood. Here, we applied whole-cell patch-clamp electrophysiology to primary hippocampal neurons and show that intracellular Aβ42 delivery leads to increased spike discharge and action potential broadening through downregulation of A-type K(+) currents. Pharmacologic studies showed that caspases and glycogen synthase kinase 3 (GSK-3) activation are required for these Aβ42-induced effects. Extracellular perfusion and subsequent internalization of Aβ42 increase spike discharge and promote GSK-3-dependent phosphorylation of the Kv4.2 α-subunit, a molecular determinant of A-type K(+) currents, at Ser-616. In acute hippocampal slices derived from an adult triple-transgenic Alzheimer's mouse model, characterized by endogenous intracellular accumulation of Aβ42, CA1 pyramidal neurons exhibit hyperexcitability accompanied by increased phosphorylation of Kv4.2 at Ser-616. Collectively, these data suggest that intraneuronal Aβ42 accumulation leads to an intracellular cascade culminating into caspases activation and GSK-3-dependent phosphorylation of Kv4.2 channels. These findings provide new insights into the toxic mechanisms triggered by intracellular Aβ42 and offer potentially new therapeutic targets for Alzheimer's disease treatment.
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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.