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Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach
Nathan P. Coles, Suzan Elsheikh, Agathe Quesnel, Lucy Butler, Claire Jennings, Chaimaa Tarzi, Ojodomo J. Achadu, Meez Islam et al.. ACS Chemical Neuroscience, 2025-01-28
Topic: Brain proteins, microglia and lab models
High Resolution Image Download MS PowerPoint Slide The aggregation of α-synuclein is crucial to the development of Lewy body diseases, including Parkinson’s disease and dementia with Lewy bodies. The aggregation pathway of α-synuclein typically involves a defined sequence of nucleation, elongation, and secondary nucleation, exhibiting prion-like spreading. This study employed Raman spectroscopy and machine learning analysis, alongside complementary techniques, to characterize the biomolecular changes during the fibrillation of purified recombinant wild-type α-synuclein protein. Monomeric α-synuclein was produced, purified, and subjected to a 7-day fibrillation assay to generate preformed fibrils. Stages of α-synuclein fibrillation were analyzed using Raman spectroscopy, with aggregation confirmed through negative staining transmission electron microscopy, mass spectrometry, and light scattering analyses. A machine learning pipeline incorporating principal component analysis and uniform manifold approximation and projection was used to analyze the Raman spectral data and identify significant peaks, resulting in differentiation between sample groups. Notable spectral shifts in α-synuclein were found in various stages of aggregation. Early changes (D1) included increases in α-helical structures (1303, 1330 cm –1 ) and β-sheet formation (1045 cm –1 ), with reductions in COO – and CH 2 bond regions (1406, 1445 cm –1 ). By D4, these structural shifts persist with additional β-sheet features. At D7, a decrease in β-sheet H-bonding (1625 cm –1 ) and tyrosine ring breathing (830 cm –1 ) indicates further structural stabilization, suggesting a shift from initial helical structures to stabilized β-sheets and aggregated fibrils. Additionally, alterations in peaks related to tyrosine, alanine, proline, and glutamic acid were identified, emphasizing the role of these amino acids in intramolecular interactions during the transition from α-helical to β-sheet conformational states in α-synuclein fibrillation. This approach offers insight into α-synuclein aggregation, enhancing the understanding of its role in Lewy body disease pathophysiology and potential diagnostic relevance.
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APA 7th
Coles, N. P., Elsheikh, S., Quesnel, A., Butler, L., Jennings, C., Tarzi, C., et al. (2025). Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach. ACS Chemical Neuroscience. https://doi.org/10.1021/acschemneuro.4c00726
Vancouver
Coles NP, Elsheikh S, Quesnel A, Butler L, Jennings C, Tarzi C, et al. Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach. ACS Chemical Neuroscience. 2025. doi:10.1021/acschemneuro.4c00726. PMID: 39875340.
BibTeX
@article{coles2025-39875340,
author = {Coles, Nathan P. and Elsheikh, Suzan and Quesnel, Agathe and Butler, Lucy and Jennings, Claire and Tarzi, Chaimaa and Achadu, Ojodomo J. and Islam, Meez and others},
title = {{Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach}},
journal = {ACS Chemical Neuroscience},
year = {2025},
doi = {10.1021/acschemneuro.4c00726},
pmid = {39875340},
url = {https://doi.org/10.1021/acschemneuro.4c00726}
}
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Key findings
- A machine learning pipeline incorporating principal component analysis and uniform manifold approximation and projection was used to analyze the Raman spectral data and identify significant peaks, resulting in differentiation between sample groups.
Why it matters
This laboratory study used Raman spectroscopy and machine learning to track how purified alpha-synuclein protein clumps together over seven days, a process relevant to Lewy body diseases such as dementia with Lewy bodies. It is early, in-vitro work and does not test any treatment, prevention or cure in people.
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Study details
- Evidence strengthLow
How this study scored 40/100
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 (ACS Chemical Neuroscience) |
| Journal's citation record | 1 / 4 | ACS Chemical Neuroscience: journal h-index 124 (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 | 4 / 5 | 2025 — within 3 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 | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ahmad Adam Khundakar: h-index 22 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Göttingen: institution h-index 934 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39875340) |
| Free to read | 2 / 2 | Free to read |
| Total | 40 / 100 | — |
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Read the original
- DOI: 10.1021/acschemneuro.4c00726
- PubMed: 39875340
- Original source →
- Free full text: ACS Chemical Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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