ArticleMolecular neurodegeneration2012
Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer's disease.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis.Scientific data · 2021Pooled it
- Peak alpha frequency and spectral exponent in postoperative delirium: a high-density EEG cohort study.BJA open · 2026Article
- Blood transcriptomic signatures link β-amyloid deposition to molecular pathways across SCD, MCI, and dementia.Frontiers in aging neuroscience · 2026Article
- Hyperpolarization-Activated Channel 1 Modulates Resilience and Susceptibility to Social Avoidance Induced by Witnessing Social Defeat Stress.Biological psychiatry · 2025Article
- Role of Ion Channels in Alzheimer's Disease Pathophysiology.The Journal of membrane biology · 2025Review
- HCN2 deficiency correlates with memory deficits and hyperexcitability of dCA1 pyramidal neurons in Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Review
- Integrated multimodal cell atlas of Alzheimer's disease.Nature neuroscience · 2024Article
- Tau-mediated synaptic dysfunction is coupled with HCN channelopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations.Aging and disease · 2024Review
- Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.Frontiers in neuroanatomy · 2024Review
- Integrated multimodal cell atlas of Alzheimer's disease.Research square · 2023Article
- Effect of ivabradine on cognitive functions of rats with scopolamine-induced dementia.Scientific reports · 2022Article
- Alzheimer's disease and epilepsy: An increasingly recognized comorbidity.Frontiers in aging neuroscience · 2022Review
- Chronic Administrations of Guanfacine on Mesocortical Catecholaminergic and Thalamocortical Glutamatergic Transmissions.International journal of molecular sciences · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice.Biology of sex differences · 2020Article
- Cardiac and neuronal HCN channelopathies.Pflugers Archiv : European journal of physiology · 2020Review
- Cohort study of electroencephalography markers of amyloid-tau-neurodegeneration pathology.Brain communications · 2020Article
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOne of the best-characterized causative factors of Alzheimer's disease (AD) is the generation of amyloid-β peptide (Aβ). AD subjects are at high risk of epileptic seizures accompanied by aberrant neuronal excitability, which in itself enhances Aβ generation. However, the molecular linkage between epileptic seizures and Aβ generation in AD remains unclear.
resultsX11 and X11-like (X11L) gene knockout mice suffered from epileptic seizures, along with a malfunction of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Genetic ablation of HCN1 in mice and HCN1 channel blockage in cultured Neuro2a (N2a) cells enhanced Aβ generation. Interestingly, HCN1 levels dramatically decreased in the temporal lobe of cynomolgus monkeys (Macaca fascicularis) during aging and were significantly diminished in the temporal lobe of sporadic AD patients.
conclusionBecause HCN1 associates with amyloid-β precursor protein (APP) and X11/X11L in the brain, genetic deficiency of X11/X11L may induce aberrant HCN1 distribution along with epilepsy. Moreover, the reduction in HCN1 levels in aged primates may contribute to augmented Aβ generation. Taken together, HCN1 is proposed to play an important role in the molecular linkage between epileptic seizures and Aβ generation, and in the aggravation of sporadic 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.