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Structures of α-synuclein filaments from human brains with Lewy pathology
Yang Y, Shi Y, Schweighauser M, Zhang X, Kotecha A, Murzin AG, Garringer HJ, Cullinane PW et al.. Nature, 2022-09-15
Topic: Brain proteins, microglia and lab models
Parkinson's disease (PD) is the most common movement disorder, with resting tremor, rigidity, bradykinesia and postural instability being major symptoms 1 . Neuropathologically, it is characterized by the presence of abundant filamentous inclusions of α-synuclein in the form of Lewy bodies and Lewy neurites in some brain cells, including dopaminergic nerve cells of the substantia nigra 2 . PD is increasingly recognised as a multisystem disorder, with cognitive decline being one of its most common non-motor symptoms. Many patients with PD develop dementia more than 10 years after diagnosis 3 . PD dementia (PDD) is clinically and neuropathologically similar to dementia with Lewy bodies (DLB), which is diagnosed when cognitive impairment precedes parkinsonian motor signs or begins within one year from their onset 4 . In PDD, cognitive impairment develops in the setting of well-established PD. Besides PD and DLB, multiple system atrophy (MSA) is the third major synucleinopathy 5 . It is characterized by the presence of abundant filamentous α-synuclein inclusions in brain cells, especially oligodendrocytes (Papp-Lantos bodies). We previously reported the electron cryo-microscopy structures of two types of α-synuclein filament extracted from the brains of individuals with MSA 6 . Each filament type is made of two different protofilaments. Here we report that the cryo-electron microscopy structures of α-synuclein filaments from the brains of individuals with PD, PDD and DLB are made of a single protofilament (Lewy fold) that is markedly different from the protofilaments of MSA. These findings establish the existence of distinct molecular conformers of assembled α-synuclein in neurodegenerative disease.
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APA 7th
Yang, Y., Shi, Y., Schweighauser, M., Zhang, X., Kotecha, A., Murzin, A. G., et al. (2022). Structures of α-synuclein filaments from human brains with Lewy pathology. Nature. https://doi.org/10.1038/s41586-022-05319-3
Vancouver
Yang Y, Shi Y, Schweighauser M, Zhang X, Kotecha A, Murzin AG, et al. Structures of α-synuclein filaments from human brains with Lewy pathology. Nature. 2022. doi:10.1038/s41586-022-05319-3. PMID: 36108674.
BibTeX
@article{yang2022-36108674,
author = {Yang, Y. and Shi, Y. and Schweighauser, M. and Zhang, X. and Kotecha, A. and Murzin, A. G. and Garringer, H. J. and Cullinane, P. W. and others},
title = {{Structures of α-synuclein filaments from human brains with Lewy pathology}},
journal = {Nature},
year = {2022},
doi = {10.1038/s41586-022-05319-3},
pmid = {36108674},
url = {https://doi.org/10.1038/s41586-022-05319-3}
}
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Key findings
- These findings establish the existence of distinct molecular conformers of assembled α-synuclein in neurodegenerative disease.
Why it matters
This study reports the cryo-electron microscopy structures of α-synuclein filaments from human brains with Lewy pathology, establishing the existence of distinct molecular conformers of assembled α-synuclein in neurodegenerative disease. The work concerns Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies and multiple system atrophy, and is structural biology rather than a treatment, cure or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 64/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 481 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 80.2 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 6 / 6 | Cited 44.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 4 / 4 | Cited 372 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Michel Goedert: h-index 147 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36108674) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
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Read the original
- DOI: 10.1038/s41586-022-05319-3
- PubMed: 36108674
- Original source →
- Free full text: IUScholarWorks (Indiana University) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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