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MCC950 suppresses NLRP3-dependent neuroinflammation and ameliorates cognitive decline in a rat model of cerebral small vessel disease
Meiyan Zhang, Xiaoyan Lan, Yue Gao, Shen Li, Guanda Qiao, Yajie Liang, Mirosław Janowski, Piotr Walczak et al.. Neural Regeneration Research, 2025-06-19
Topic: Brain proteins, microglia and lab models
JOURNAL/nrgr/04.03/01300535-202606000-00056/figure1/v/2026-02-11T151048Z/r/image-tiff Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia. However, there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease. In this study, we investigated the potential therapeutic effects of MCC950, a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor, on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats. Our results showed that chronic administration of MCC950 (10 mg/kg) to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation, thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors, including interleukin-1β and -18. A decrease in astrocytic and microglial activation was also observed. We also found that MCC950 significantly inhibited autophagy. More importantly, behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function, which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain, such as blood‒brain barrier breakdown, white matter damage, and endothelial dysfunction. Thus, our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhang, M., Lan, X., Gao, Y., Li, S., Qiao, G., Liang, Y., et al. (2025). MCC950 suppresses NLRP3-dependent neuroinflammation and ameliorates cognitive decline in a rat model of cerebral small vessel disease. Neural Regeneration Research. https://doi.org/10.4103/nrr.nrr-d-24-01055
Vancouver
Zhang M, Lan X, Gao Y, Li S, Qiao G, Liang Y, et al. MCC950 suppresses NLRP3-dependent neuroinflammation and ameliorates cognitive decline in a rat model of cerebral small vessel disease. Neural Regeneration Research. 2025. doi:10.4103/nrr.nrr-d-24-01055. PMID: 40537012.
BibTeX
@article{zhang2025-40537012,
author = {Zhang, Meiyan and Lan, Xiaoyan and Gao, Yue and Li, Shen and Qiao, Guanda and Liang, Yajie and Janowski, Mirosław and Walczak, Piotr and others},
title = {{MCC950 suppresses NLRP3-dependent neuroinflammation and ameliorates cognitive decline in a rat model of cerebral small vessel disease}},
journal = {Neural Regeneration Research},
year = {2025},
doi = {10.4103/nrr.nrr-d-24-01055},
pmid = {40537012},
url = {https://doi.org/10.4103/nrr.nrr-d-24-01055}
}
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
- Our results showed that chronic administration of MCC950 (10 mg/kg) to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation, thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors, including interleukin-1β and -18.
- We also found that MCC950 significantly inhibited autophagy.
- More importantly, behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function, which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain, such as blood‒brain barrier breakdown, white matter damage, and endothelial dysfunction.
- Thus, our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.
Why it matters
In spontaneously hypertensive rats, the NLRP3 inhibitor MCC950 suppressed inflammasome activation and inflammation and improved cognitive function along with brain pathology. This is animal research, so it does not yet show that MCC950 treats cerebral small vessel disease or dementia in people.
Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neural Regeneration Research) |
| Journal's citation record | 1 / 4 | Neural Regeneration Research: journal h-index 100 (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 | Laboratory or animal study (title names “rat”) — scores zero |
| 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 | 2 / 6 | Cited 2.1× 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 | 1 / 4 | Last-listed author Chengyan Chu: h-index 18 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Maryland, Baltimore: institution h-index 970 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40537012) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.4103/nrr.nrr-d-24-01055
- PubMed: 40537012
- Original source →
- Free full text: Neural Regeneration Research →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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