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Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia
Adnan Akif, T.T. Nguyen, Langni Liu, Xiaotian Xu, Amol A. Kulkarni, Jianxiong Jiang, Yang Zhang, Jiukuan Hao. Fluids and Barriers of the CNS, 2025-06-03
Topic: Brain proteins, microglia and lab models
AMS-17 treatment improved cognitive function, enhanced blood-brain barrier (BBB) integrity, and promoted remyelination in VaD mice. Additionally, AMS-17 reduced neurodegeneration and decreased the expression of NLRP3 and its associated proteins, Apoptosis-associated speck-like protein (ASC), and cleaved caspase-1 in the brain. It also lowered pro-inflammatory TNF-α and IL-1β levels, while increasing the anti-inflammatory IL-4 level in the blood. The findings of this study provide the first promising evidence for the use of AMS-17 in VaD treatment in mice. This study introduces AMS-17 as a novel chemical scaffold with NLRP3 inhibitory activity, which can be further developed for the treatment of VaD in humans. CLINICAL TRIAL NUMBER: Not applicable.
Key findings
- AMS-17 treatment improved cognitive function, enhanced blood-brain barrier (BBB) integrity, and promoted remyelination in VaD mice.
- Additionally, AMS-17 reduced neurodegeneration and decreased the expression of NLRP3 and its associated proteins, Apoptosis-associated speck-like protein (ASC), and cleaved caspase-1 in the brain.
- It also lowered pro-inflammatory TNF-α and IL-1β levels, while increasing the anti-inflammatory IL-4 level in the blood.
- The findings of this study provide the first promising evidence for the use of AMS-17 in VaD treatment in mice.
- This study introduces AMS-17 as a novel chemical scaffold with NLRP3 inhibitory activity, which can be further developed for the treatment of VaD in humans.
Why it matters
In mice with vascular dementia, the compound AMS-17 improved cognitive function and reduced markers of inflammation and neurodegeneration. These are early animal findings, and the authors state AMS-17 needs further development before it could be tested for treating vascular dementia in humans.
Study details
- Evidence strengthLow
How this study scored 41/100
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 (Fluids and Barriers of the CNS) |
| Journal's citation record | 1 / 4 | Fluids and Barriers of the CNS: journal h-index 86 (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 | 3 / 7 | Cited 16 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.9× 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 | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Jiukuan Hao: h-index 16 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The University of Texas Health Science Center at Houston: institution h-index 756 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40462117) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s12987-025-00665-6
- PubMed: 40462117
- Original source →
- Free full text: Fluids and Barriers of the CNS →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Akif, A., Nguyen, T., Liu, L., Xu, X., Kulkarni, A. A., Jiang, J., et al. (2025). Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia. Fluids and Barriers of the CNS. https://doi.org/10.1186/s12987-025-00665-6
Vancouver
Akif A, Nguyen T, Liu L, Xu X, Kulkarni AA, Jiang J, et al. Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia. Fluids and Barriers of the CNS. 2025. doi:10.1186/s12987-025-00665-6. PMID: 40462117.
BibTeX
@article{akif2025-40462117,
author = {Akif, Adnan and Nguyen, T.T. and Liu, Langni and Xu, Xiaotian and Kulkarni, Amol A. and Jiang, Jianxiong and Zhang, Yang and Hao, Jiukuan},
title = {{Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia}},
journal = {Fluids and Barriers of the CNS},
year = {2025},
doi = {10.1186/s12987-025-00665-6},
pmid = {40462117},
url = {https://doi.org/10.1186/s12987-025-00665-6}
}
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