ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Broad-spectrum effects of 4-aminopyridine to modulate amyloid beta1-42-induced cell signaling and functional responses in human microglia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 67 citations in OpenAlex.
- Trial
- Stabilizing a mammalian RNA thermometer confers neuroprotection in subarachnoid hemorrhage.Nature communications · 2025Article
- 4-aminopyridine exerts anxiolytic and pro-cognitive effects in mice model of medial prefrontal cortex ischemia.Metabolic brain disease · 2025Article
- Role of Ion Channels in Alzheimer's Disease Pathophysiology.The Journal of membrane biology · 2025Review
- Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [International journal of molecular sciences · 2024Article
- A novelFrontiers in cellular neuroscience · 2024Article
- Neuroprotective Properties of 4-Aminopyridine.Neurology(R) neuroimmunology & neuroinflammation · 2021Review
- Roles of Microglial Ion Channel in Neurodegenerative Diseases.Journal of clinical medicine · 2021Review
- K channel blockage with 3,4-diaminopyridine potentiates the effect of L-DOPA on dopamine release in striatal slices prepared from 6-OHDA pre-treated rats.Experimental brain research · 2020Article
- High-content imaging of 3D-cultured neural stem cells on a 384-pillar plate for the assessment of cytotoxicity.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Mechanisms by which fibroblast growth factor 20 improves motor performance in a mouse model of Parkinson's disease.Neural regeneration research · 2019Article
- Article
- Microglia in Alzheimer's Disease: A Role for Ion Channels.Frontiers in neuroscience · 2018Review
- Article
- Blockade of fast A-type and TEA-sensitive potassium channels provide an antiparkinsonian effect in a 6-OHDA animal model.Neurosciences (Riyadh, Saudi Arabia) · 2017Article
- The mixed-lineage kinase 3 inhibitor URMC-099 facilitates microglial amyloid-β degradation.Journal of neuroinflammation · 2016Article
- Pharmacological antagonism of interleukin-8 receptor CXCR2 inhibits inflammatory reactivity and is neuroprotective in an animal model of Alzheimer's disease.Journal of neuroinflammation · 2015Article
- Neuroinflammation in Alzheimer's disease: chemokines produced by astrocytes and chemokine receptors.International journal of clinical and experimental pathology · 2014Review
- Correlated inflammatory responses and neurodegeneration in peptide-injected animal models of Alzheimer's disease.BioMed research international · 2014Review
- Microglial TNF-α-dependent elevation of MHC class I expression on brain endothelium induced by amyloid-beta promotes T cell transendothelial migration.Neurochemical research · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We investigated the modulating actions of the nonselective K(+) channel blocker 4-aminopyridine (4-AP) on amyloid beta (Abeta(1-42))-induced human microglial signaling pathways and functional processes. Whole-cell patch-clamp studies showed acute application of Abeta(1-42) (5 mum) to human microglia led to rapid expression of a 4-AP-sensitive, non-inactivating outwardly rectifying K(+) current (I(K)). Intracellular application of the nonhydrolyzable analog of GTP, GTPgammaS, induced an outward K(+) current with similar properties to the Abeta(1-42)-induced I(K) including sensitivity to 4-AP (IC(50) = 5 mm). Reverse transcriptase-PCR showed a rapid expression of a delayed rectifier Kv3.1 channel in Abeta(1-42)-treated microglia. Abeta(1-42) peptide also caused a slow, progressive increase in levels of [Ca(2+)](i) (intracellular calcium) that was partially blocked by 4-AP. Chronic exposure of human microglia to Abeta(1-42) led to enhanced p38 mitogen-activated protein kinase and nuclear factor kappaB expression with factors inhibited by 4-AP. Abeta(1-42) also induced the expression and production of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha, the chemokine IL-8, and the enzyme cyclooxygenase-2; 4-AP was effective in reducing all of these pro-inflammatory mediators. Additionally, toxicity of supernatant from Abeta(1-42)-treated microglia on cultured rat hippocampal neurons was reduced if 4-AP was included with peptide. In vivo, injection of Abeta(1-42) into rat hippocampus induced neuronal damage and increased microglial activation. Daily administration of 1 mg/kg 4-AP was found to suppress microglial activation and exhibited neuroprotection. The overall results suggest that 4-AP modulation of an Abeta(1-42)-induced I(K) (candidate channel Kv3.1) and intracellular signaling pathways in human microglia could serve as a therapeutic strategy for neuroprotection in Alzheimer's disease pathology.
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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.