ArticleActa neuropathologica communications2018
Rapid dissemination of alpha-synuclein seeds through neural circuits in an in-vivo prion-like seeding experiment.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 84 citations in OpenAlex.
- A Biological Framework for Parkinson's Disease: Advances in α-Synuclein-Centered Biomarkers and Staging.Journal of neurochemistry · 2026Review
- Distinct Molecular Mechanisms Underlie Modulation of Seeded α-Synuclein Aggregation and Toxicity by Salvianolic Acid B and Dihydromyricetin.International journal of molecular sciences · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Microstructural alterations of parafascicular nucleus pathways associated with freezing of gait in Parkinson's disease.Brain communications · 2026Article
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lewy body diseases and the gut.Molecular neurodegeneration · 2025Review
- Mitochondrial dysfunction in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Pathologic Substrates of Structural Brain Network Resilience and Topology in Parkinson Disease Decedents.Neurology · 2024Article
- Role of Lipids in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Effects of local reduction of endogenous α-synuclein using antisense oligonucleotides on the fibril-induced propagation of pathology through the neural network in wild-type mice.Acta neuropathologica communications · 2024Article
- Lysosomal storage, impaired autophagy and innate immunity in Gaucher and Parkinson's diseases: insights for drug discovery.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- α-Synuclein: A Promising Biomarker for Parkinson's Disease and Related Disorders.Journal of movement disorders · 2024Article
- Glial senescence enhances α-synuclein pathology owing to its insufficient clearance caused by autophagy dysfunction.Cell death discovery · 2024Article
- Impaired neuronal activity as a potential factor contributing to the underdeveloped cerebrovasculature in a young Parkinson's disease mouse model.Scientific reports · 2023Article
- Feed-forward metabotropic signaling by Cav1 CaNeurobiology of disease · 2023Article
- Review
- Altered Distribution of SNARE Proteins in Primary Neurons Exposed to Different Alpha-Synuclein Proteoforms.Cellular and molecular neurobiology · 2023Article
- Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons.Toxicon : official journal of the International Society on Toxinology · 2023Article
- Propagative α-synuclein seeds as serum biomarkers for synucleinopathies.Nature medicine · 2023Article
- α-Synuclein Preformed Fibrils Bind to β-Neurexins and Impair β-Neurexin-Mediated Presynaptic Organization.Cells · 2023Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Accumulating evidence suggests that the lesions of Parkinson's disease (PD) expand due to transneuronal spreading of fibrils composed of misfolded alpha-synuclein (a-syn), over the course of 5-10 years. However, the precise mechanisms and the processes underlying the spread of these fibril seeds have not been clarified in vivo. Here, we investigated the speed of a-syn transmission, which has not been a focus of previous a-syn transmission experiments, and whether a-syn pathologies spread in a neural circuit-dependent manner in the mouse brain. We injected a-syn preformed fibrils (PFFs), which are seeds for the propagation of a-syn deposits, either before or after callosotomy, to disconnect bilateral hemispheric connections. In mice that underwent callosotomy before the injection, the propagation of a-syn pathology to the contralateral hemisphere was clearly reduced. In contrast, mice that underwent callosotomy 24 h after a-syn PFFs injection showed a-syn pathology similar to that seen in mice without callosotomy. These results suggest that a-syn seeds are rapidly disseminated through neuronal circuits immediately after seed injection, in a prion-like seeding experiment in vivo, although it is believed that clinical a-syn pathologies take years to spread throughout the brain. In addition, we found that botulinum toxin B blocked the transsynaptic transmission of a-syn seeds by specifically inactivating the synaptic vesicle fusion machinery. This study offers a novel concept regarding a-syn propagation, based on the Braak hypothesis, and also cautions that experimental transmission systems may be examining a unique type of transmission, which differs from the clinical disease state.
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