ArticleCurrent biology : CB2014
α-synuclein multimers cluster synaptic vesicles and attenuate recycling.
Article in Current biology : CB, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.
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Who cites it
181 citing papers in PubMed, 275 citations in OpenAlex.
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Increased Expression of α-Synuclein Impairs Trafficking of the Essential SNARE Protein Synaptobrevin-2.Journal of neurochemistry · 2026Article
- Nanoscale CabioRxiv : the preprint server for biology · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- A split biotin ligase approach reveals proteins associated with oligomeric alpha-synuclein during aggregation.Scientific reports · 2026Article
- When Proteins Go MAD-Misfolded, Amplified, Detected: Advances in α-Synuclein Pathophysiology and RT-QuIC Detection.Molecular neurobiology · 2026Review
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Optogenetic-induced α-synuclein accumulation reveals early synaptic dysfunction in experimental models of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- Pathological and Functional Brain Amyloids: A New Concept Explaining the Differences.International journal of molecular sciences · 2025Review
- Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis.Journal of molecular cell biology · 2025Review
- A Split Biotin Ligase Approach to Revealing Proteins Associated with Oligomeric Alpha-Synuclein During Aggregation.Research square · 2025Article
- Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.The Journal of physiology · 2025Article
- DDHD2 provides a flux of saturated fatty acids for neuronal energy and function.Nature metabolism · 2025Article
- GDNF attenuates a-synuclein aggregation-induced damage to VTA-NAc dopaminergic transmission and alleviates depression-like behaviors in mice.Scientific reports · 2025Article
- Physical and Mechanical Properties of Monomeric Alpha-Synuclein Provide Leads to Molecular Function.The journal of physical chemistry. B · 2025Article
- Stearoyl-CoA desaturase inhibition normalizes brain lipid saturation, α-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice.JCI insight · 2025Article
- α-Synuclein-Assembled Synaptic Vesicle Pools at the Presynaptic Terminal: A Study of α-Synuclein Function Using a Novel Mouse Model.Acta histochemica et cytochemica · 2025Review
- Differential pathological dynamics triggered by distinct Parkinson patient-derived α-synuclein extracts in nonhuman primates.Science advances · 2025Article
- Vimentin network dysregulation mediates neurite deficits inScience advances · 2025Article
121 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The normal functions and pathologic facets of the small presynaptic protein α-synuclein (α-syn) are of exceptional interest. In previous studies, we found that α-syn attenuates synaptic exo/endocytosis; however, underlying mechanisms remain unknown. More recent evidence suggests that α-syn exists as metastable multimers and not solely as a natively unfolded monomer. However, conformations of α-syn at synapses--its physiologic locale--are unclear, and potential implications of such higher-order conformations to synaptic function are unknown. Exploring α-syn conformations and synaptic function in neurons, we found that α-syn promptly organizes into physiological multimers at synapses. Furthermore, our experiments indicate that α-syn multimers cluster synaptic vesicles and restrict their motility, suggesting a novel role for these higher-order structures. Supporting this, α-syn mutations that disrupt multimerization also fail to restrict synaptic vesicle motility or attenuate exo/endocytosis. We propose a model in which α-syn multimers cluster synaptic vesicles, restricting their trafficking and recycling, and consequently attenuate neurotransmitter release.
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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.