ArticleProceedings of the National Academy of Sciences of the United States of America2015
Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 135 citations in OpenAlex.
- Molecular Signaling Pathways in Depression and Neuroinflammation: Focus on New Pathophysiological Proteins and Therapeutic Compounds.Antioxidants (Basel, Switzerland) · 2026Review
- Mechanisms of increased Alzheimer's disease pathology with R47H and R62H TREM2 variants.Acta neuropathologica · 2026Article
- Article
- Elevated NaInternational journal of molecular sciences · 2026Article
- Review
- Elevated NabioRxiv : the preprint server for biology · 2025Article
- Serotonergic Regulation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer's Pathogenesis.Molecular neurobiology · 2025Review
- Factors that influence the Na/K-ATPase signaling and function.Frontiers in pharmacology · 2025Review
- Review
- Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.Aging and disease · 2024Review
- Neuronal autosis is NaCell death & disease · 2024Article
- Disease Mechanisms of Multiple System Atrophy: What a Parallel Between the Form of Pasta and the Alpha-Synuclein Assemblies Involved in MSA and PD Tells Us.Cerebellum (London, England) · 2024Review
- Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction-the trigger for PANoptosis in neurons.Frontiers in aging neuroscience · 2024Review
- Article
- In Silico Analysis Reveals the Modulation of Ion Transmembrane Transporters in the Cerebellum of Alzheimer's Disease Patients.International journal of molecular sciences · 2023Article
- Tau and Amyloid β Protein in Patient-Derived Aqueous Brain Extracts Act Concomitantly to Disrupt Long-Term PotentiationThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- SorCS1 inhibits amyloid-β binding to neurexin and rescues amyloid-β-induced synaptic pathology.Life science alliance · 2023Article
- A Peptide-Conjugated Probe with Cleavage-Induced Morphological Change for Treatment on Tumor Cell Membrane.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges.Biophysics and physicobiology · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 15 institutions in 4 countries.
Funding
Abstract
Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the molecular identities of pathogenic amyloid β-protein (Aβ) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10- to 15-nm spherical Aβ oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na(+)/K(+)-ATPase α3 subunit (NAKα3). ASPD-binding to NAKα3 impaired NAKα3-specific activity, activated N-type voltage-gated calcium channels, and caused mitochondrial calcium dyshomeostasis, tau abnormalities, and neurodegeneration. NMR and molecular modeling studies suggested that spherical ASPD contain N-terminal-Aβ-derived "thorns" responsible for target binding, which are distinct from low molecular-weight oligomers and dodecamers. The fourth extracellular loop (Ex4) region of NAKα3 encompassing Asn(879) and Trp(880) is essential for ASPD-NAKα3 interaction, because tetrapeptides mimicking this Ex4 region bound to the ASPD surface and blocked ASPD neurotoxicity. Our findings open up new possibilities for knowledge-based design of peptidomimetics that inhibit neurodegeneration in AD by blocking aberrant ASPD-NAKα3 interaction.
Indexed as
Identifiers
What OpenQuestion holds
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.