ArticleThe EMBO journal2015
α-synuclein assemblies sequester neuronal α3-Na+/K+-ATPase and impair Na+ gradient.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 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
123 citing papers in PubMed, 209 citations in OpenAlex.
- Differential proteostasis imbalance and the molecular basis of distinct synucleinopathies and tauopathies.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Deletion or immunotherapeutic blockade of FcγRIIb (CD32b) impairs α-Syn propagation in vivo.Acta neuropathologica · 2026Article
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- Article
- Anti-TLR2 immunotherapy modulates neuron-to-oligodendrocyte propagation of α-synuclein in mouse and human models.Nature communications · 2026Article
- Sodium disrupts mitochondrial energy metabolism to execute NECSO.Nature communications · 2025Article
- Extracellular LCN2 Binding to 24p3R in Astrocytes Impedes α-Synuclein Endocytosis in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Assessment of the Behavioral and Neurochemical Characteristics in a Mice Model of the Premotor Stage of Parkinson's Disease Induced by Chronic Administration of a Low Dose of MPTP.International journal of molecular sciences · 2025Article
- Parkinson's paradox: alpha-synuclein's selective strike on SNc dopamine neurons over VTA.NPJ Parkinson's disease · 2025Article
- Unveiling the role of Na⁺/K⁺-ATPase pump: neurodegenerative mechanisms and therapeutic horizons.Pharmacological reports : PR · 2025Review
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.Molecular neurodegeneration · 2025Review
- Neuronal LAG3 facilitates pathogenic α-synuclein neuron-to-neuron propagation.bioRxiv : the preprint server for biology · 2025Article
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- Exploring α-synuclein Interaction Partners and their Potential Clinical Implications for Parkinson's Disease.Neurochemical research · 2024Article
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- α-Synuclein strain propagation is independent of cellular prion protein expression in a transgenic synucleinopathy mouse model.PLoS pathogens · 2024Article
- Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein.Nature communications · 2024Article
- 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
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular α-synuclein (α-syn) assemblies can be up-taken by neurons; however, their interaction with the plasma membrane and proteins has not been studied specifically. Here we demonstrate that α-syn assemblies form clusters within the plasma membrane of neurons. Using a proteomic-based approach, we identify the α3-subunit of Na+/K+-ATPase (NKA) as a cell surface partner of α-syn assemblies. The interaction strength depended on the state of α-syn, fibrils being the strongest, oligomers weak, and monomers none. Mutations within the neuron-specific α3-subunit are linked to rapid-onset dystonia Parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). We show that freely diffusing α3-NKA are trapped within α-syn clusters resulting in α3-NKA redistribution and formation of larger nanoclusters. This creates regions within the plasma membrane with reduced local densities of α3-NKA, thereby decreasing the efficiency of Na+ extrusion following stimulus. Thus, interactions of α3-NKA with extracellular α-syn assemblies reduce its pumping activity as its mutations in RDP/AHC.
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.