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The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration
Mahul-Mellier AL, Burtscher J, Maharjan N, Weerens L, Croisier M, Kuttler F, Leleu M, Knott GW et al.. Proceedings of the National Academy of Sciences of the United States of America, 2020-02-19
Topic: Brain proteins, microglia and lab models
Parkinson's disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, the processes that govern α-syn fibrillization and LB formation remain poorly understood. In this work, we sought to dissect the spatiotemporal events involved in the biogenesis of the LBs at the genetic, molecular, biochemical, structural, and cellular levels. Toward this goal, we further developed a seeding-based model of α-syn fibrillization to generate a neuronal model that reproduces the key events leading to LB formation, including seeding, fibrillization, and the formation of inclusions that recapitulate many of the biochemical, structural, and organizational features of bona fide LBs. Using an integrative omics, biochemical and imaging approach, we dissected the molecular events associated with the different stages of LB formation and their contribution to neuronal dysfunction and degeneration. In addition, we demonstrate that LB formation involves a complex interplay between α-syn fibrillization, posttranslational modifications, and interactions between α-syn aggregates and membranous organelles, including mitochondria, the autophagosome, and endolysosome. Finally, we show that the process of LB formation, rather than simply fibril formation, is one of the major drivers of neurodegeneration through disruption of cellular functions and inducing mitochondria damage and deficits, and synaptic dysfunctions. We believe that this model represents a powerful platform to further investigate the mechanisms of LB formation and clearance and to screen and evaluate therapeutics targeting α-syn aggregation and LB formation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mahul-Mellier, A. L., Burtscher, J., Maharjan, N., Weerens, L., Croisier, M., Kuttler, F., et al. (2020). The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1913904117
Vancouver
Mahul-Mellier AL, Burtscher J, Maharjan N, Weerens L, Croisier M, Kuttler F, et al. The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America. 2020. doi:10.1073/pnas.1913904117. PMID: 32075919.
BibTeX
@article{mahulmellier2020-32075919,
author = {Mahul-Mellier, A. L. and Burtscher, J. and Maharjan, N. and Weerens, L. and Croisier, M. and Kuttler, F. and Leleu, M. and Knott, G. W. and others},
title = {{The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2020},
doi = {10.1073/pnas.1913904117},
pmid = {32075919},
url = {https://doi.org/10.1073/pnas.1913904117}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Using an integrative omics, biochemical and imaging approach, we dissected the molecular events associated with the different stages of LB formation and their contribution to neuronal dysfunction and degeneration.
Why it matters
In a lab-grown neuron model built to mimic how Lewy bodies form, this study found that formation is not just α-synuclein clumping into fibrils: it also involves chemical modification of the protein and its entanglement with cell structures including mitochondria, the autophagosome and the endolysosome. The authors conclude that this whole formation process, rather than fibrils alone, "is one of the major drivers of neurodegeneration." This is a Parkinson's-framed cell study, not a human or treatment study, so it points to mechanisms worth testing rather than anything patients or families can act on directly.
Study details
- Evidence strengthLow
How this study scored 55/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 2 / 5 | 2020 — within 10 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 705 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 88.1 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 5 / 6 | Cited 38.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 4 / 4 | Cited 300 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Hilal Ahmed Lashuel: h-index 92 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | École Polytechnique Fédérale de Lausanne: institution h-index 1,186 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32075919) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1073/pnas.1913904117
- PubMed: 32075919
- Original source →
- Free full text: Proceedings of the National Academy of Sciences →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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