ArticleThe Journal of biological chemistry2019
Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Experimental models of gut-first Parkinson's disease: A systematic review.Neurogastroenterology and motility · 2023Pooled it
- A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Impairment in stimulus-response learning as a cognitive biomarker in a model of synucleinopathy.Translational psychiatry · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Cellular prion protein levels modulate nigrostriatal vulnerability to α-synuclein oligomers in Parkinson's disease.Frontiers in neuroscience · 2026Article
- STIP1/HOP promotes the formation of cytotoxic α-synuclein oligomers.Molecular neurodegeneration advances · 2026Article
- Hidden faces of alpha-synuclein: Cryo-EM revelation of fibril polymorphs driven by disease, mutations, and PTMs.BBA advances · 2026Review
- Lack of functional STING modulates immunity but does not protect dopaminergic neurons in the alpha-synuclein pre-formed fibrils Parkinson's disease mouse model.NPJ Parkinson's disease · 2025Article
- Cellular prion protein and calcium ions trigger the neurotoxicity of α-synuclein aggregates.Cell & bioscience · 2025Article
- Modulation of O-GlcNAc cycling influences α-synuclein amplification, degradation, and associated neuroinflammatory pathology.Molecular neurodegeneration · 2025Article
- Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease.Nature neuroscience · 2025Article
- Oligomeric alpha-synuclein causes early synaptic dysfunction of the corticostriatal pathway associated with non-motor symptoms.NPJ Parkinson's disease · 2025Article
- Early α-synuclein aggregation decreases corticostriatal glutamate drive and synapse density.Neurobiology of disease · 2025Article
- A mechanistic model of pure and lipidic α-synuclein aggregation for advancing Parkinson's therapies.Communications chemistry · 2025Article
- Female mice exhibit resistance to disease progression despite early pathology in a transgenic mouse model inoculated with alpha-synuclein fibrils.Communications biology · 2025Article
- Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- RT-QuIC: a highly promising diagnostic method for neurodegenerative diseases-advantages and limitations.Frontiers in neurology · 2025Review
- Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases.Science advances · 2024Article
- Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice.NPJ Parkinson's disease · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions composed of aggregated α-synuclein (α-syn). These inclusions are associated with behavioral and pathological PD phenotypes. One strategy for therapeutic interventions is to prevent the formation of these inclusions to halt disease progression. α-Synuclein exists in multiple structural forms, including disordered, nonamyloid oligomers, ordered amyloid oligomers, and fibrils. It is critical to understand which conformers contribute to specific PD phenotypes. Here, we utilized a mouse model to explore the pathological effects of stable β-amyloid-sheet oligomers compared with those of fibrillar α-synuclein. We biophysically characterized these species with transmission EM, atomic-force microscopy, CD spectroscopy, FTIR spectroscopy, analytical ultracentrifugation, and thioflavin T assays. We then injected these different α-synuclein forms into the mouse striatum to determine their ability to induce PD-related phenotypes. We found that β-sheet oligomers produce a small but significant loss of dopamine neurons in the substantia nigra pars compacta (SNc). Injection of small β-sheet fibril fragments, however, produced the most robust phenotypes, including reduction of striatal dopamine terminals, SNc loss of dopamine neurons, and motor-behavior defects. We conclude that although the β-sheet oligomers cause some toxicity, the potent effects of the short fibrillar fragments can be attributed to their ability to recruit monomeric α-synuclein and spread
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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.