ArticleMediators of inflammation2026
Mechanisms of Microglial NLRP3 Inflammasome Activation by Methylmalonic Acid in Methylmalonic Acidemia.
Article in Mediators of inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Mechanisms of Microglial NLRP3 Inflammasome Activation by Methylmalonic Acid in Methylmalonic Acidemia.Mediators of inflammation · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundMicroglial activation is a critical pathogenic mechanism of neurological damage in methylmalonic acidemia (MMA). The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is closely associated with neuroinflammatory processes. However, the mechanism of NLRP3 inflammasome activation in microglia by methylmalonic acid (MMAcid) remains unclear.
methodsMouse microglia BV2 cells and hippocampal neuronal HT22 cells were stimulated with different concentrations of MMAcid. Neuronal cells were treated with conditioned medium derived from differently treated microglia. Microscopy was used to observe morphological changes of cells. Cell counting kit-8 (CCK-8) assay was performed to assess cell viability (VB). In addition, the mRNA and protein levels were detected via qRT-PCR, ELISA, and western blot. To further validate the mechanism, we used lentivirus infection and small interfering RNA (siRNA) transfection to overexpress (OE) and knockdown (KD) extracellular signal-regulated kinase (ERK) and analyzed the inflammatory pathway.
resultsDirect exposure of neuronal cells to MMAcid significantly reduced cell VB, accompanied by morphological features suggestive of pyroptosis. MMAcid activated microglia, which was accompanied by increased expression of inflammatory molecules, activation of the ERK/nuclear factor-κB (NF-κB)/NLRP3 signaling pathway, and elevated secretion of interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α). Neuronal cell VB decreased when cocultured with the supernatant from MMAcid-treated microglia. Overexpression of ERK further enhanced microglial activation and potentiated MMA-induced neuronal pyroptosis-related signaling. Conversely, knocking down ERK expression in microglia reduced their activation by MMAcid and decreased cytokine secretion, but it did not completely reverse MMA-induced neuronal damage.
conclusionMMAcid is associated with microglial activation, accompanied by alterations in the ERK/NF-κB/NLRP3 signaling pathway and increased release of inflammatory cytokines, which may contribute to neuronal pyroptosis-related changes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.