ArticleNature communications2024
Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
24.0field-weighted citation impact, top 1% of its field
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
50 citing papers in PubMed, 65 citations in OpenAlex.
- Brain-seeded 42-residue Amyloid-β Fibrils That Resemble Fibrils Directly Extracted From Alzheimer's Disease Brain Tissue.Journal of molecular biology · 2026Article
- In Vitro-Prepared A30P Alpha-Synuclein Fibrils Adopt the Conserved and Disease-Relevant Greek Key Fold.The journal of physical chemistry. B · 2026Article
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- PET imaging of alpha-synuclein: from radiotracer design through in vitro and in vivo translation.European journal of nuclear medicine and molecular imaging · 2026Review
- Cracking the code of native amyloid fibrils: advances and next steps to enable pathology-informed therapeutic and diagnostic.Nature structural & molecular biology · 2026Review
- Article
- Formation of Condition-Dependent Alpha-Synuclein Fibril Strain in Artificial Cerebrospinal Fluid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Top-Down Scoring of Spectral Fitness by Image Analysis for Protein Structure Validation.Journal of chemical information and modeling · 2026Article
- When Proteins Go MAD-Misfolded, Amplified, Detected: Advances in α-Synuclein Pathophysiology and RT-QuIC Detection.Molecular neurobiology · 2026Review
- From dynamic condensates to pathological assemblies: the phase behavior of tau andFrontiers in molecular neuroscience · 2026Review
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- A novel lncRNA FAM151B-DT regulates degradation of aggregation prone proteins.Molecular psychiatry · 2025Article
- MAS Cryoprobe Enhances Solid-State NMR Signals of α-Synuclein Fibrils.bioRxiv : the preprint server for biology · 2025Article
- Alpha-Synuclein Neurobiology in Parkinson's Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives.Brain sciences · 2025Review
- Interactions of Neurodegenerative Disease Positron Emission Tomography Imaging Probe Candidates with the C-Terminus of α-Synuclein Fibrils.Chembiochem : a European journal of chemical biology · 2025Article
- α-Synuclein purification significantly impacts seed amplification assay performance and consistency.Acta neuropathologica communications · 2025Article
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
- Design and application of a Tau seed amplification assay for screening inhibitors of Tau seeding.Alzheimer's research & therapy · 2025Article
- Identification of small molecule dimethyoxyphenyl piperazine inhibitors of alpha-synuclein fibril growth.Scientific reports · 2025Article
- Article
Corrections and comments
- Update of
Authors and funding
23 authors at 5 institutions in 1 country.
Dhruva D Dhavale *Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0002-0096-1085
Alexander M Barclay *Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Collin G BorcikDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Katherine BasoreCenter for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Deborah A BertholdDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Isabelle R GordonDepartment of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Jialu LiuDepartment of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Moses H MilchbergDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Jennifer Y O'SheaDepartment of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0002-5492-1847
Michael J RauCenter for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0001-5170-2000
Zachary SmithDepartment of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Soumyo SenTheoretical and Computational Biophysics Group, NIH Resource for Macromolecular Modeling and Visualization, Beckman Institute for Advanced Science and Technology, Department of Biochemistry, and Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Brock SummersCenter for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.
John SmithDepartment of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Owen A WarmuthDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Richard J PerrinDepartment of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0002-3443-7716
Joel S PerlmutterDepartment of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-3263-8917
Qian ChenDepartment of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.ORCID http://orcid.org/0000-0002-1968-441X
James A J FitzpatrickCenter for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0002-7907-3602
Charles D SchwietersComputational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Emad TajkhorshidTheoretical and Computational Biophysics Group, NIH Resource for Macromolecular Modeling and Visualization, Beckman Institute for Advanced Science and Technology, Department of Biochemistry, and Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.ORCID http://orcid.org/0000-0001-8434-1010
Chad M RienstraCenter for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. crienstra@wisc.edu.ORCID http://orcid.org/0000-0002-9912-5596
Paul T KotzbauerDepartment of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA. kotzbauerp@wustl.edu.
Hope Center for Neurological Disorders · USUniversity of Illinois Urbana-Champaign · USWashington University in St. Louis · USUniversity of Wisconsin–Madison · USNational Institutes of Health · US
Funding
INVESTIGATIONS OF DEMENTIA IN PARKINSON DISEASER01NS075321 · NINDS · WASHINGTON UNIVERSITY · PI CAMPBELL, MEGHAN C, PERLMUTTER, JOEL SYNES · 2011 to 2021
$8.2MTechnologies for Solid-State NMR Data CollectionP41GM136463 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI WESTLER, WILLIAM MILO · 2021 to 2025
$6.4MResource for Macromolecular Modeling and VisualizationR24GM145965 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Emad Tajkhorshid · 2022 to 2026
$6.2MProtein Aggregation and Neurotransmitter Deficits in Parkinson DiseaseR01NS097799 · NINDS · WASHINGTON UNIVERSITY · PI PAUL T KOTZBAUER · 2016 to 2026
$5.8MStructural Biology of Alpha-Synuclein in Lewy Body DementiaRF1NS110436 · NINDS · WASHINGTON UNIVERSITY · PI KOTZBAUER, PAUL T, RIENSTRA, CHAD M · 2023 to 2023
$4.2MSTRUCTURAL BIOLOGY OF ALPHA-SYNUCLEIN IN LEWY BODY DEMENTIAU01NS110436 · NINDS · WASHINGTON UNIVERSITY · PI KOTZBAUER, PAUL T · 2018 to 2022
$4.1MInvestigations of Dementia in Parkinson DiseaseRF1NS075321 · NINDS · WASHINGTON UNIVERSITY · PI CAMPBELL, MEGHAN C, PERLMUTTER, JOEL SYNES · 2023 to 2023
$2.3MPredoctoral Training in Molecular BiophysicsT32GM130550 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SENES, ALESSANDRO · 2019 to 2023
$1.5MStructural Biology and Biophysics of Alpha-Synuclein Fibrils by Solid-State NMRF32GM149118 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BORCIK, COLLIN GRIFFIN · 2023 to 2024
$143kNIGMS NIH HHS F32 GM149118NIGMS NIH HHS P41 GM136463NIGMS NIH HHS R24 GM145965NIGMS NIH HHS T32 GM130550NINDS NIH HHS R01 NS075321NINDS NIH HHS R01 NS097799NINDS NIH HHS RF1 NS075321NINDS NIH HHS RF1 NS110436NINDS NIH HHS U01 NS110436
Abstract
The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.
Indexed as
Lewy Body DiseaseParkinson Diseasealpha-SynucleinCryoelectron MicroscopyHumansLewy Bodiesalpha-SynucleinSNCA protein, human
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
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.