ArticlePloS one2018
Sequestration of synaptic proteins by alpha-synuclein aggregates leading to neurotoxicity is inhibited by small peptide.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Effect of Aggregated Alpha Synuclein on Synaptic and Axonal Proteins in Parkinson's Disease-A Systematic Review.Biomolecules · 2022Pooled it
- Review
- A single-domain antibody targets aggregation-prone region of α-synuclein to reduce synucleinopathy, rescue neurodegeneration and improve function.bioRxiv : the preprint server for biology · 2026Article
- α-Synuclein Pathology Spreads in a Midbrain-Hindbrain Assembloid Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dopaminergic changes in the subgenual cingulate cortex in dementia with lewy bodies associates with presence of depression.Translational psychiatry · 2025Article
- The Relationship between SNAP25 and Some Common Human Neurological Syndromes.Current pharmaceutical design · 2024Review
- Vascular and Nonvascular Mechanisms of Cognitive Impairment and Dementia.Clinics in geriatric medicine · 2023Review
- α-Synuclein Disrupts Vesicle Fusion by Two Mutant-Specific Mechanisms.Molecules and cells · 2022Article
- Focused Ultrasound-Induced Blood-Brain Barrier Opening Enhanced α-Synuclein Expression in Mice for Modeling Parkinson's Disease.Pharmaceutics · 2022Article
- Sequestration of the exocytic SNARE Psy1 into multiprotein nodes reinforces polarized morphogenesis in fission yeast.Molecular biology of the cell · 2021Article
- Review
- Parkinson mice show functional and molecular changes in the gut long before motoric disease onset.Molecular neurodegeneration · 2021Article
- Role of SNAREs in Neurodegenerative Diseases.Cells · 2021Review
- Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders.Frontiers in aging neuroscience · 2021Review
- Presynaptic accumulation of α-synuclein causes synaptopathy and progressive neurodegeneration inBrain communications · 2021Article
- Enhancing the Astrocytic Clearance of Extracellular α-Synuclein Aggregates by Ginkgolides Attenuates Neural Cell Injury.Cellular and molecular neurobiology · 2019Article
- Novel Mannitol-Based Small Molecules for Inhibiting Aggregation of α-Synuclein Amyloids in Parkinson's Disease.Frontiers in molecular biosciences · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Synuclein (α-syn) is a major component of Lewy bodies found in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Under the pathological conditions, α-syn tends to generate a diverse form of aggregates showing toxicity to neuronal cells and able to transmit across cells. However, mechanisms by which α-syn aggregates affect cytotoxicity in neurons have not been fully elucidated. Here we report that α-syn aggregates preferentially sequester specific synaptic proteins such as vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 (SNAP25) through direct binding which is resistant to SDS. The sequestration effect of α-syn aggregates was shown in a cell-free system, cultured primary neurons, and PD mouse model. Furthermore, we identified a specific blocking peptide derived from VAMP2 which partially inhibited the sequestration by α-syn aggregates and contributed to reduced neurotoxicity. These results provide a mechanism of neurotoxicity mediated by α-syn aggregates and suggest that the blocking peptide interfering with the pathological role of α-syn aggregates could be useful for designing a potential therapeutic drug for the treatment of PD.
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