ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
α-Synuclein (αSyn) Preformed Fibrils Induce Endogenous αSyn Aggregation, Compromise Synaptic Activity and Enhance Synapse Loss in Cultured Excitatory Hippocampal Neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 115 citations in OpenAlex.
- Soluble α-synuclein oligomers drive transient corticostriatal pathology and delayed nigral vulnerability in a mouse model of early α-synucleinopathy.Acta neuropathologica communications · 2026Article
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- Accelerated and localized synucleinopathy in a hybrid mouse model: implications for positron emission tomography studies.Npj imaging · 2026Article
- Identification of pesticides associated with an increased risk of Parkinson's disease using a multi-screen approach.Environment international · 2026Article
- Systematic evaluation of mitochondrial morphology regulators for amelioration of neuronal α-synucleinopathy.NPJ Parkinson's disease · 2026Article
- Microengineering of the capillary interface of midbrain dopaminergic neurons to study Parkinson's disease vascular alterations.Communications engineering · 2026Article
- Direct current stimulation induced reduction in α-synuclein in primary neurons: targeting Parkinson's disease.Brain communications · 2026Article
- Disrupting α-Synuclein-ClpP interaction restores mitochondrial function and attenuates neuropathology in Parkinson's disease models.Molecular neurodegeneration · 2025Article
- Backtracking α-synuclein pathology: social deficits precede motor symptoms in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Common Mechanism Underlying Synaptic Dysfunction Caused by Preformed Fibril-Induced Accumulation of α-Synuclein or Tau in a Culture Propagation Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Dynein-Dependent Endo-Lysosomal Degradation Drives Lewy Body Disorders Accompanied by Aβ Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cortical α-synuclein pathology induces cell autonomous neuronal hypoactivity and compensatory circuit changes in a model of early Lewy body dementia.bioRxiv : the preprint server for biology · 2025Article
- Early α-synuclein aggregation decreases corticostriatal glutamate drive and synapse density.Neurobiology of disease · 2025Article
- Parkinson disease-associated toxic exposures selectively up-regulate vesicular glutamate transporter vGlut2 in a model of human cortical neurons.Molecular biology of the cell · 2025Article
- Motor cortical neuronal hyperexcitability associated with α-synuclein aggregation.NPJ Parkinson's disease · 2025Article
- Site-specific seeding of Lewy pathology induces distinct pre-motor cellular and dendritic vulnerabilities in the cortex.Nature communications · 2024Article
- Genetically modified E. Coli secreting melanin (E.melanin) activates the astrocytic PSAP-GPR37L1 pathway and mitigates the pathogenesis of Parkinson's disease.Journal of nanobiotechnology · 2024Article
- α-Synuclein disrupts microglial autophagy through STAT1-dependent suppression of Ulk1 transcription.Journal of neuroinflammation · 2024Article
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Motor Cortical Neuronal Hyperexcitability Associated with α-Synuclein Aggregation.Research square · 2024Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
Synucleinopathies are characterized by the accumulation of insoluble α-synuclein (αSyn). To test whether αSyn aggregates modulate synaptic activity, we used a recently developed model in primary neurons for inducing αSyn pathology. We demonstrated that preformed fibrils (PFFs) generated with recombinant human αSyn compromised synaptic activity in a time- and dose-dependent manner and that the magnitude of these deficits correlated with the formation of αSyn pathology in cultured excitatory hippocampal neurons from both sexes of mice. Remarkably, acute passive infusion of αSyn PFFs from whole-cell patch-clamp pipette decreased mEPSC frequency within 10 min followed by induction of αSyn pathology within 1 d. Moreover, by direct addition of αSyn PFFs into culture medium, the formation of misfolded αSyn inclusions dramatically compromised the colocalization of synaptic markers and altered dynamic changes of dendritic spines, but the viability of neurons was not affected up to 7 d post-treatment with αSyn PFFs. Our data indicate that intraneuronal αSyn fibrils impaired the initiation of synaptogenesis and their physiological functions, thereby suggesting that targeting synaptic dysfunction in synucleinopathies may provide a promising therapeutic direction.
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