ArticleScience advances2022
A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed.
- O-GlcNAcylation: A molecular switch linking brain health to neurodegeneration.Neural regeneration research · 2026Article
- Genetics of α-Synuclein: The Prime Pathological Player of Parkinson's Disease.Neurotoxicity research · 2026Review
- Dual effect of α-synuclein disease variants on condensate formation.Nature communications · 2026Article
- Modeling Parkinson's pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.Science advances · 2026Article
- Gut microbiota-derived succinate links proteostasis collapse to α-synuclein pathology and aging.iScience · 2026Article
- STIP1/HOP promotes the formation of cytotoxic α-synuclein oligomers.Molecular neurodegeneration advances · 2026Article
- Hydrophobic residues in the α-synuclein NAC domain drive seed-competent fibril formation and are targeted by peptide inhibitors.The FEBS journal · 2026Article
- Mapping the Role of Monomer Conformation in the Amyloid Formation of α-Synuclein Splice Variants.Journal of the American Chemical Society · 2025Article
- ZnJournal of the American Chemical Society · 2025Article
- Defined human tri-lineage brain microtissues.bioRxiv : the preprint server for biology · 2025Article
- Amyloid formation of alternatively spliced variants of α-synuclein.Protein science : a publication of the Protein Society · 2025Article
- Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach.ACS chemical neuroscience · 2025Article
- Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases.Science advances · 2024Article
- Structurally targeted mutagenesis identifies key residues supporting α-synuclein misfolding in multiple system atrophy.Journal of Parkinson's disease · 2024Article
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Article
- O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology.Nature chemical biology · 2024Article
- Liquid-liquid phase separation of α-synuclein is highly sensitive to sequence complexity.Protein science : a publication of the Protein Society · 2024Article
- Ultrastructures of α-Synuclein Filaments in Synucleinopathy Brains and Experimental Models.Journal of movement disorders · 2024Article
- Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases.NPJ Parkinson's disease · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The alpha-synuclein mutation E83Q, the first in the NAC domain of the protein, was recently identified in a patient with dementia with Lewy bodies. We investigated the effects of this mutation on the aggregation of aSyn monomers and the structure, morphology, dynamic, and seeding activity of the aSyn fibrils in neurons. We found that it markedly accelerates aSyn fibrillization and results in the formation of fibrils with distinct structural and dynamic properties. In cells, this mutation is associated with higher levels of aSyn, accumulation of pS129, and increased toxicity. In a neuronal seeding model of Lewy body (LB) formation, the E83Q mutation significantly enhances the internalization of fibrils into neurons, induces higher seeding activity, and results in the formation of diverse aSyn pathologies, including the formation of LB-like inclusions that recapitulate the immunohistochemical and morphological features of brainstem LBs observed in brains of patients with Parkinson's disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.