ArticleMolecular neurobiology2025
NLRC5-Mediated Epigenetic and Proteomic Regulation of Microglial Panoptosis Drives Neuroinflammation in Multiple Sclerosis.
Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Microglial dysfunction contributes to multiple sclerosis (MS) pathogenesis, yet the link between epigenetic regulation and inflammatory cell death (PANoptosis) remains unclear. This study explores NOD-like receptor family CARD domain containing 5 (NLRC5) as a regulator of microglial PANoptosis in MS. Transcriptomic data from experimental autoimmune encephalomyelitis (EAE) microglia (GSE253318) and GEO datasets (GSE78809, GSE154228) were integrated to identify PANoptosis-related genes. Mendelian randomization (MR) linked NLRC5 expression to proteomic targets using UK Biobank and deCODE Iceland protein quantitative trait loci (pQTLs). Methylation quantitative trait locus (mQTL) analysis assessed MS-associated CpG sites. Lipopolysaccharide (LPS)-treated BV2 microglial models were used to validate NLRC5-PANoptosome assembly via Western blot and immunofluorescence. NLRC5 was identified as a hub gene in PANoptosis-related pathways. MR suggested modest associations between NLRC5 expression and apoptotic (GABA Type A Receptor-Associated Protein (GABARAP), BR Serine/Threonine Kinase 2 (BRSK2), TNF Superfamily Member 12 (TNFSF12)) and apoptotic/necroptotic (BCL2) effectors, consistent across inverse-variance weighted (IVW), Bayesian weighted Mendelian randomization (BWMR), and generalized summary-data-based Mendelian randomization (GSMR) methods, though effect sizes were small. Hypermethylation of NLRC5 (cg04097610) showed a potential protective association with MS risk (odds ratio (OR) = 0.885, P = 0.039). In vitro, LPS stimulation upregulated NLRC5, ZBP1, ASC, and caspase-8, supporting PANoptosome activation. NLRC5 may regulate microglial PANoptosis through epigenetic and proteomic mechanisms, linking inflammatory cell death to MS progression. These findings suggest NLRC5 as a candidate regulator and potential therapeutic target, although further validation in human studies is required.
Indexed as
Identifiers
41313522What Socratic 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 Socratic graph.