ArticleActa neuropathologica communications2019
α-Synuclein conformational strains spread, seed and target neuronal cells differentially after injection into the olfactory bulb.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 114 citations in OpenAlex.
- From aggregate structure to disease trajectory: the role of the proteostasis network.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- Microengineering of the capillary interface of midbrain dopaminergic neurons to study Parkinson's disease vascular alterations.Communications engineering · 2026Article
- Hidden faces of alpha-synuclein: Cryo-EM revelation of fibril polymorphs driven by disease, mutations, and PTMs.BBA advances · 2026Review
- Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation.NPJ Parkinson's disease · 2025Article
- Ligands for Protein Fibrils of Amyloid-β, α-Synuclein, and Tau.Chemical reviews · 2025Review
- Positron emission tomography tracers for synucleinopathies.Molecular neurodegeneration · 2025Review
- Article
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Aptamer binding footprints discriminate α-synuclein fibrillar polymorphs from different synucleinopathies.Nucleic acids research · 2024Article
- LRRK2-Associated Parkinsonism With and WithoutmedRxiv : the preprint server for health sciences · 2024Article
- Effect of host and strain factors on α-synuclein prion pathogenesis.Trends in neurosciences · 2024Review
- A multiverse of α-synuclein: investigation of prion strain properties with carboxyl-terminal truncation specific antibodies in animal models.Acta neuropathologica communications · 2024Article
- Alpha-synuclein aggregates are phosphatase resistant.Acta neuropathologica communications · 2024Article
- Neither alpha-synuclein fibril strain nor host murine genotype influences seeding efficacy.NPJ Parkinson's disease · 2024Article
- Ligand Profiling as a Diagnostic Tool to Differentiate Patient-Derived α-Synuclein Polymorphs.ACS chemical neuroscience · 2024Article
- Alpha-synuclein aggregates are phosphatase resistant.bioRxiv : the preprint server for biology · 2024Article
- Parkinson's disease-derived α-synuclein assemblies combined with chronic-type inflammatory cues promote a neurotoxic microglial phenotype.Journal of neuroinflammation · 2024Article
- Disease Mechanisms of Multiple System Atrophy: What a Parallel Between the Form of Pasta and the Alpha-Synuclein Assemblies Involved in MSA and PD Tells Us.Cerebellum (London, England) · 2024Review
- Liquid-liquid phase separation and conformational strains ofFrontiers in molecular neuroscience · 2024Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Alpha-synuclein inclusions, the hallmarks of synucleinopathies, are suggested to spread along neuronal connections in a stereotypical pattern in the brains of patients. Ample evidence now supports that pathological forms of alpha-synuclein propagate in cell culture models and in vivo in a prion-like manner. However, it is still not known why the same pathological protein targets different cell populations, propagates with different kinetics and leads to a variety of diseases (synucleinopathies) with distinct clinical features. The aggregation of the protein alpha-synuclein yields different conformational polymorphs called strains. These strains exhibit distinct biochemical, physical and structural features they are able to imprint to newly recruited alpha-synuclein. This had led to the view that the clinical heterogeneity observed in synucleinopathies might be due to distinct pathological alpha-synuclein strains.To investigate the pathological effects of alpha-synuclein strains in vivo, we injected five different pure strains we generated de novo (fibrils, ribbons, fibrils-65, fibrils-91, fibrils-110) into the olfactory bulb of wild-type female mice. We demonstrate that they seed and propagate pathology throughout the olfactory network within the brain to different extents. We show strain-dependent inclusions formation in neurites or cell bodies. We detect thioflavin S-positive inclusions indicating the presence of mature amyloid aggregates.In conclusion, alpha-synuclein strains seed the aggregation of their cellular counterparts to different extents and spread differentially within the central nervous system yielding distinct propagation patterns. We provide here the proof-of-concept that the conformation adopted by alpha-synuclein assemblies determines their ability to amplify and propagate in the brain in vivo. Our observations support the view that alpha-synuclein polymorphs may underlie different propagation patterns within human brains.
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