ArticleProceedings of the National Academy of Sciences of the United States of America2015
Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. 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 435 papers, 1 of them a synthesis that pooled it.
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Who cites it
435 citing papers in PubMed, 1 synthesis or guideline pooled it, 697 citations in OpenAlex.
- Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.Frontiers in aging neuroscience · 2022Pooled it
- Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson's Disease: A Randomized, Placebo-Controlled, Phase 1 Study.Journal of Parkinson's disease · 2021Trial
- α-Synuclein strain homogeneity in multiple system atrophy subtypes.Brain pathology (Zurich, Switzerland) · 2026Article
- Connexin 50 mediates disease-relevant alpha-synuclein oligomer propagation and neuroinflammation in neurodegenerative disease.iScience · 2026Article
- Adaptation of α-synuclein fibrils following multiple system atrophy transmission to mice.bioRxiv : the preprint server for biology · 2026Article
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α‑Synuclein, and Aβ40.JACS Au · 2026Article
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- 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
- When Proteins Go MAD-Misfolded, Amplified, Detected: Advances in α-Synuclein Pathophysiology and RT-QuIC Detection.Molecular neurobiology · 2026Review
- Hidden faces of alpha-synuclein: Cryo-EM revelation of fibril polymorphs driven by disease, mutations, and PTMs.BBA advances · 2026Review
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Pathogens Association with Alzheimer Disease: Emerging Concepts and New Perspectives.Current gene therapy · 2026Review
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Residue-Specific Modulation of Aggregation-Associated Interactions by Spermine in Tau, α-Synuclein, and Aβ40.bioRxiv : the preprint server for biology · 2025Article
- mGluR4-NPDC1 complex mediates α-synuclein fibril-induced neurodegeneration.Nature communications · 2025Article
- Review
- Seed amplification of MSA alpha-synuclein aggregates preserves the biological and structural properties of brain-derived aggregates.Nature communications · 2025Article
- Cellular prion protein and calcium ions trigger the neurotoxicity of α-synuclein aggregates.Cell & bioscience · 2025Article
- Article
375 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Prions are proteins that adopt alternative conformations that become self-propagating; the PrP(Sc) prion causes the rare human disorder Creutzfeldt-Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of α-synuclein. To determine whether human α-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing full-length, mutant human α-synuclein fused to yellow fluorescent protein (α-syn140*A53T-YFP) and TgM83(+/-) mice expressing α-synuclein (A53T). The TgM83(+/-) mice that were hemizygous for the mutant transgene did not develop spontaneous illness; in contrast, the TgM83(+/+) mice that were homozygous developed neurological dysfunction. Brain extracts from 14 MSA cases all transmitted neurodegeneration to TgM83(+/-) mice after incubation periods of ∼120 d, which was accompanied by deposition of α-synuclein within neuronal cell bodies and axons. All of the MSA extracts also induced aggregation of α-syn*A53T-YFP in cultured cells, whereas none of six Parkinson's disease (PD) extracts or a control sample did so. Our findings argue that MSA is caused by a unique strain of α-synuclein prions, which is different from the putative prions causing PD and from those causing spontaneous neurodegeneration in TgM83(+/+) mice. Remarkably, α-synuclein is the first new human prion to be identified, to our knowledge, since the discovery a half century ago that CJD was transmissible.
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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.