ArticleNature2015
α-Synuclein strains cause distinct synucleinopathies after local and systemic administration.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 651 papers.
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Who cites it
651 citing papers in PubMed, 1,126 citations in OpenAlex.
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial Quality Control Imbalance in the Heterogeneity of Parkinson's Disease: From Selective Vulnerability to Stratified Transformation.International journal of molecular sciences · 2026Review
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- α-Synuclein strain homogeneity in multiple system atrophy subtypes.Brain pathology (Zurich, Switzerland) · 2026Article
- Duodenal α-Synuclein PFF Injection Induces Vagus-Related Gut-to-Brain Pathology in C57BL/6J and A53T Transgenic Mice.Brain sciences · 2026Article
- From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease.Metabolic brain disease · 2026Review
- Blood-Based α-Synuclein Biomarkers in Parkinson's Disease: Molecular Diversity, Analytical Advances and Clinical Translation.International journal of molecular sciences · 2026Review
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- Modest improvement of metabolic and behavioral deficits with long-term ambroxol treatment in a Pink1Acta pharmacologica Sinica · 2026Article
- Live cell imaging of exogenous α-synuclein fibrils in primary microglia and neuron co-cultures.Biochemistry and biophysics reports · 2026Article
- Association between α-synuclein in plasma neuron-derived exosomes and clinical symptoms in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Mapping cellular vulnerability in Parkinson's disease using retro-AAVs and preformed α-synuclein fibrils.Translational neurodegeneration · 2026Article
- Interactions Between Nutraceuticals and α-Synuclein Conformational States: Molecular Mechanisms and Neuroprotective Implications in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Biochemical signatures of skin α-synuclein in synucleinopathies revealed by RT-QuIC assay end-product analysis.Acta neuropathologica · 2026Article
- Microengineering of the capillary interface of midbrain dopaminergic neurons to study Parkinson's disease vascular alterations.Communications engineering · 2026Article
- Seed amplification of released alpha-synuclein strains reveals genotype-specific differences in Parkinson's disease neurons.Frontiers in aging neuroscience · 2026Article
- Article
- Pollutants regulate changes in pathological markers of neurodegenerative diseases: a new perspective in environmental toxicology.Frontiers in toxicology · 2026Review
- Hydrophobic residues in the α-synuclein NAC domain drive seed-competent fibril formation and are targeted by peptide inhibitors.The FEBS journal · 2026Article
- Exidavnemab binds to aggregated α-synuclein in human brains affected by α-synucleinopathies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
591 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson's disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.
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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.