Topic: Gut, metabolism and diet
Sulforaphane (SFN), a natural isothiocyanate from cruciferous vegetables, exerts neuroprotective effects through mechanisms extending beyond canonical Nrf2/ARE activation. Here, we developed a multi-dataset computational framework integrating transcriptomic analysis, multi-criteria target prioritization, and structural docking evaluation. R- and S-SFN were docked against 693 prioritized targets using AutoDock Vina, followed by cross-validation, brain expression profiling, and molecular dynamics simulations. Four genes (IGSF9, KCNQ5, KCTD12, and NFIX) were dysregulated across all four datasets. Among 693 targets, 88 showed favorable predicted docking scores (ΔG ≤ −4.0 kcal/mol), with 65 (73.9%) exhibiting expression in at least one GTEx brain region. Independent cross-validation showed significant enrichment of prioritized targets in an SFN-responsive Alzheimer’s disease transcriptomic dataset (OR = 1.44, 95% CI: 1.08–1.89, p = 0.0104). Complementary disease gene set enrichment confirmed that 33% of strong hits (29/88) overlap established neurodegeneration gene sets across AD, PD, and ALS — including ACHE,target of FDA-approved anti-AD drugs — with highly significant enrichment across all three disease categories (OR range: 67–127, all p < 0.001). R-SFN showed a modest but statistically detectable preference over S-SFN across the 88 strong hits (Wilcoxon p = 0.0081; paired t-test p = 0.0047). TMEM45A, GRIK2, and FABP3 emerged as putative neurodegeneration-relevant targets. Molecular dynamics simulations supported the structural stability of R-SFN poses for TMEM45A, GRIK2, and FABP3, while MM-GBSA estimated favorable binding energies for GRIK2 (ΔG_bind = −19.78 kcal/mol) and FABP3 (ΔG_bind = −14.49 kcal/mol). These findings generate testable hypotheses regarding previously underexplored molecular targets that may contribute to the neuroprotective actions of SFN.
Key findings
- Independent cross-validation showed significant enrichment of prioritized targets in an SFN-responsive Alzheimer’s disease transcriptomic dataset (OR = 1.44, 95% CI: 1.08–1.89, p = 0.0104).
- Complementary disease gene set enrichment confirmed that 33% of strong hits (29/88) overlap established neurodegeneration gene sets across AD, PD, and ALS — including ACHE,target of FDA-approved anti-AD drugs — with highly significant enrichment across all three disease categories (OR range: 67–127, all p < 0.001).
- These findings generate testable hypotheses regarding previously underexplored molecular targets that may contribute to the neuroprotective actions of SFN.
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Study details
- Effect size73.9%; OR = 1.44
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 26 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 16 of the 62 points we could judge it on, which is 26 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 16 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 16 of the 62 points we could judge it on is 26 out of 100. |
| Total | 26 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Ugur, S., & Onal Suzek, T. (2026). Integrated Transcriptomic and Structural Prioritization of Sulforaphane Targets in Neurodegeneration: A Multi-Dataset In Silico Study. bioRxiv. https://doi.org/10.64898/2026.10.20.760417
Vancouver
Ugur S, Onal Suzek T. Integrated Transcriptomic and Structural Prioritization of Sulforaphane Targets in Neurodegeneration: A Multi-Dataset In Silico Study. bioRxiv. 2026. doi:10.64898/2026.10.20.760417.
BibTeX
@article{ugur2026-bb2a526b,
author = {Ugur, S. and Onal Suzek, T.},
title = {{Integrated Transcriptomic and Structural Prioritization of Sulforaphane Targets in Neurodegeneration: A Multi-Dataset In Silico Study}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.20.760417},
url = {https://doi.org/10.64898/2026.10.20.760417}
}
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