ArticleAnnals of neurology2012
Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers.
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Who cites it
207 citing papers in PubMed, 358 citations in OpenAlex.
- Striatal blood-brain barrier permeability in Parkinson's disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Trial
- Divergent effects of pathological α-synuclein truncations and mutations on phase separation.Nature communications · 2026Article
- Soluble α-synuclein oligomers drive transient corticostriatal pathology and delayed nigral vulnerability in a mouse model of early α-synucleinopathy.Acta neuropathologica communications · 2026Article
- Tear fluid as a novel specimen for detection of alpha-synuclein seeding activity in Parkinson's disease.Scientific reports · 2026Article
- A Pathophysiological Model of Parkinson's Disease Based on Microvascular Flow Disturbance and Leukocyte-Mediated Oxidative Injury in Critical Pigmented Neuronal Niches.Antioxidants (Basel, Switzerland) · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Microfluidic platform for understanding Parkinson's disease and α-synuclein conformation.Translational neurodegeneration · 2025Review
- Optogenetic-induced α-synuclein accumulation reveals early synaptic dysfunction in experimental models of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Novel regulators of heparan sulfate proteoglycans modulate cellular uptake of α-synuclein fibrils.Communications biology · 2025Article
- Organic cation transporter 3 on neuronal mitochondria mediates MPPBMC biology · 2025Article
- N-Homocysteinylation of lysine residues in α-Synuclein enhances aggregation propensity and cytotoxicity in SH-SY5Y cells.Scientific reports · 2025Article
- Key Connectomes and Synaptic-Compartment-Specific Risk Genes Drive Pathological α-Synuclein Spreading.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Lasting Impact: Exploring the Brain Mechanisms that Link Traumatic Brain Injury to Parkinson's Disease.Molecular neurobiology · 2025Review
- Alpha-synuclein pathology and Parkinson's disease-related olfactory dysfunctions: an update on preclinical models and therapeutic approaches.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Research models to study lewy body dementia.Molecular neurodegeneration · 2025Review
- A high-fidelity microfluidic platform reveals retrograde propagation as the main mechanism of α-Synuclein spread in human neurons.NPJ Parkinson's disease · 2025Article
- Microfluidic tools to model, monitor, and modulate the gut-brain axis.Biomicrofluidics · 2025Article
- Searching for the cellular underpinnings of the selective vulnerability to tauopathic insults in Alzheimer's disease.Communications biology · 2025Article
- Novel Poly-Arginine Peptide R18D Reduces α-Synuclein Aggregation and Uptake of α-Synuclein Seeds in Cortical Neurons.Biomedicines · 2025Article
- The role of autophagy in synucleinopathy: clearance versus spread of α-synuclein.Autophagy reports · 2025Review
147 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe lesions of Parkinson disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of α-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport.
methodsWe grew primary cortical mouse neurons in microfluidic devices to separate somata from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent α-synuclein fibrils and their transfer to second-order neurons.
resultsFibrillar α-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar α-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts.
interpretationThese results support the hypothesis that the progression of Parkinson disease can be caused by neuron-to-neuron spread of α-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be trans-synaptic gives hope that α-synuclein fibrils could be intercepted by drugs during the extracellular phase of their journey.
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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.