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Structural and functional insights into the selective inhibition of mutant tau aggregation by purpurin and oleocanthal in frontotemporal dementia
Alladi Charanraj Goud, Iu P Kozlov, Patricie Skoupilová, Lukáš Malina, Sudeep Roy, Viswanath Das. Protein Science, 2025-08-27
Topic: Brain proteins, microglia and lab models
Tau aggregation driven by microtubule-associated protein tau (MAPT) mutations is central to frontotemporal dementia pathology, yet no disease-modifying therapies effectively target mutant tau. Here, we identify purpurin (PUR) and oleocanthal (OLC) as selective inhibitors of mutant tau aggregation using peptide models spanning the R2R3 interface. Biophysical and cellular assays demonstrated that both compounds more effectively inhibit the aggregation of mutant tau peptides compared to wild-type, with PUR preferentially targeting V287I and N279K variants, and OLC showing broader inhibitory activity. Surface plasmon resonance and docking analyses revealed more stable interactions and lower binding free energies with mutant tau, consistent with their enhanced inhibitory effects. Computational studies using monomeric and fibrillar tau structures supported the mutation-specific binding profiles of PUR and OLC. Atomic force microscopy and confocal imaging confirmed reduced fibril formation, while post-transduction treatment assays showed that both compounds significantly suppressed intracellular tau propagation. Additionally, OLC reduced tau phosphorylation and oligomerization in SY5Y-TauP301L-EGFP cells expressing mutant tau. These findings highlight the potential of PUR and OLC as structurally distinct, mutation-targeted inhibitors of tau aggregation and propagation, providing a rationale for their further development as candidate therapeutics for frontotemporal dementia.
Key findings
- Biophysical and cellular assays demonstrated that both compounds more effectively inhibit the aggregation of mutant tau peptides compared to wild-type, with PUR preferentially targeting V287I and N279K variants, and OLC showing broader inhibitory activity.
- Surface plasmon resonance and docking analyses revealed more stable interactions and lower binding free energies with mutant tau, consistent with their enhanced inhibitory effects.
- Atomic force microscopy and confocal imaging confirmed reduced fibril formation, while post-transduction treatment assays showed that both compounds significantly suppressed intracellular tau propagation.
- These findings highlight the potential of PUR and OLC as structurally distinct, mutation-targeted inhibitors of tau aggregation and propagation, providing a rationale for their further development as candidate therapeutics for frontotemporal dementia.
Why it matters
In laboratory peptide and cell assays, purpurin and oleocanthal inhibited aggregation of mutant tau more effectively than wild-type tau and suppressed intracellular tau propagation. These are early in-vitro findings and do not yet show a treatment, cure or prevention in people.
Study details
- Evidence strengthLow
How this study scored 37/100
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 (Protein Science) |
| Journal's citation record | 3 / 4 | Protein Science: journal h-index 250 (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 | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Viswanath Das: h-index 16 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Palacký University Olomouc: institution h-index 437 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40862394) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Goud, A. C., Kozlov, I. P., Skoupilová, P., Malina, L., Roy, S., & Das, V. (2025). Structural and functional insights into the selective inhibition of mutant tau aggregation by purpurin and oleocanthal in frontotemporal dementia. Protein Science. https://doi.org/10.1002/pro.70240
Vancouver
Goud AC, Kozlov IP, Skoupilová P, Malina L, Roy S, Das V. Structural and functional insights into the selective inhibition of mutant tau aggregation by purpurin and oleocanthal in frontotemporal dementia. Protein Science. 2025. doi:10.1002/pro.70240. PMID: 40862394.
BibTeX
@article{goud2025-40862394,
author = {Goud, Alladi Charanraj and Kozlov, Iu P and Skoupilová, Patricie and Malina, Lukáš and Roy, Sudeep and Das, Viswanath},
title = {{Structural and functional insights into the selective inhibition of mutant tau aggregation by purpurin and oleocanthal in frontotemporal dementia}},
journal = {Protein Science},
year = {2025},
doi = {10.1002/pro.70240},
pmid = {40862394},
url = {https://doi.org/10.1002/pro.70240}
}
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