ArticleMolecular neurodegeneration2018
Extracellular α-synuclein levels are regulated by neuronal activity.
Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review.Neurology · 2024Pooled it
- Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid.Annals of neurology · 2020Trial
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- α-Synuclein triggers intercellular nanotubes formation to prevent apoptosis in astroglia by promoting stemness.Cell & bioscience · 2026Article
- The Mechanism Underlying the Abnormal Expression of α-Synuclein in the Cortical Lesions of Patients With FCD Type IIb and TSC.CNS neuroscience & therapeutics · 2026Article
- Membrane interfacial potential governs surface condensation and fibrillation of α-Synuclein in neurons.Nature communications · 2026Article
- Differences in α-synuclein conformational states in physiologically relevant pH/NaThe Analyst · 2026Article
- The Progress of Active Immunotherapy for Parkinson's Disease.International journal of molecular sciences · 2026Review
- Formation of Condition-Dependent Alpha-Synuclein Fibril Strain in Artificial Cerebrospinal Fluid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Uncovering the role of c-Fos in the bidirectional relationship between depression/anxiety behaviors and α-synuclein propagation in Parkinson's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- MSN Templated with L-Dopa Amide Derivatives Outperforms the Efficiency of Free-L-Dopa in Reducing Parkinson's Behavioral Dysfunction in Mice.International journal of nanomedicine · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Dreaming of Better Treatments: Advances in Drug Development for Sleep Medicine and Chronotherapy.Journal of sleep research · 2025Review
- N-type CaNPJ Parkinson's disease · 2025Article
- Glial phagocytosis for synapse and toxic proteins in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Key Connectomes and Synaptic-Compartment-Specific Risk Genes Drive Pathological α-Synuclein Spreading.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of phospholipid saturation and composition in α-synuclein aggregation and toxicity: A dual in vitro and in vivo approach.Protein science : a publication of the Protein Society · 2025Article
- Review
- Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.Acta pharmacologica Sinica · 2025Article
- Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.Molecular neurodegeneration · 2025Review
41 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
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundα-Synuclein is a presynaptic protein abundant in the cytoplasmic compartment of neurons, whereas its presence in the extracellular space has also been observed under physiological conditions. Extracellular α-synuclein has pathological significance, exhibiting cellular toxicity and impairment of synaptic transmission. Notably, misfolded α-synuclein drives the cell-to-cell propagation of pathology via the extracellular space. However, the primary mechanism that regulates the extracellular levels of α-synuclein remains to be determined.
methodsUsing several mechanistically distinct methods to modulate neuronal/synaptic activities in primary neuronal culture and in vivo microdialysis, we examined the involvement of neuronal/synaptic activities on α-synuclein release.
resultsWe demonstrate here that physiological release of endogenous α-synuclein highly depends on intrinsic neuronal activities. Elevating neuronal activity rapidly increased, while blocking activity decreased, α-synuclein release. In vivo microdialysis experiments in freely moving mice revealed that ~ 70% of extracellular α-synuclein arises from neuronal activity-dependent pathway. Selective modulation of glutamatergic neurotransmission altered extracellular α-synuclein levels, implicating this specific neuronal network in the mechanism of activity-dependent release of α-synuclein. While neuronal activity tightly regulated α-synuclein release, elevated synaptic vesicle exocytosis per se was capable to elicit α-synuclein release. We also found that extracellular α-synuclein exists as high molecular weight species.
conclusionsThe present study uncovers a novel regulatory pathway associated with α-synuclein release, whose dysregulation might affect various pathological actions of extracellular α-synuclein including its trans-synaptic propagation.
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.