Related Experiment Video

Updated: Feb 22, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

21.4K

A new mechanism regulating microglial NLRP3 inflammasome: FMR1 mediates NLRP3 mRNA stability

Qian Deng1, Qianqian Bai2, Yang Yang2

  • 1Department of Pharmacy, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China.

Plos One
|February 20, 2026
PubMed
Abstract

Insights

Fragile X mental retardation homolog 1 (FMR1) suppresses NLRP3 inflammasome activation in multiple sclerosis (MS) models by destabilizing NLRP3 mRNA, offering therapeutic potential for MS by regulating neuroinflammation.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • The NLRP3 inflammasome is implicated in chronic inflammation and multiple sclerosis (MS) pathogenesis.
  • Microglia play a key role in neuroinflammation, and their activation is central to MS.
  • Understanding NLRP3 regulation in microglia is crucial for developing MS therapies.

Purpose of the Study:

  • To investigate a novel post-transcriptional regulatory mechanism of NLRP3 expression in microglia.
  • To determine the role of FMR1 in controlling NLRP3 inflammasome activation.
  • To explore the therapeutic potential of FMR1 in MS models.

Main Methods:

  • Established an experimental autoimmune encephalomyelitis (EAE) mouse model of MS.
  • Utilized lentivirus-mediated overexpression of FMR1 in EAE mice and BV2 microglial cells.
  • Stimulated BV2 cells with lipopolysaccharide (LPS) and adenosine triphosphate (ATP).
  • Assessed mRNA and protein levels using qPCR, western blot, and immunohistochemistry.
  • Quantified caspase-1 activity and IL-1β/IL-18 levels.
  • Identified RNA-binding proteins interacting with NLRP3 mRNA via RNA pull-down and mass spectrometry.
  • Analyzed NLRP3 mRNA stability using Actinomycin D.

Main Results:

  • NLRP3 inflammasome activation was confirmed in EAE mice and stimulated BV2 cells.
  • FMR1 overexpression in EAE mice reduced microglial activation (IBA-1) and NLRP3 expression.
  • FMR1 directly interacted with the 3' UTR of NLRP3 mRNA, leading to its destabilization.
  • FMR1 suppressed NLRP3 protein expression and inhibited NLRP3 inflammasome activation.

Conclusions:

  • FMR1 acts as a suppressor of NLRP3 inflammasome activation by destabilizing NLRP3 mRNA.
  • FMR1 demonstrates therapeutic potential for MS by modulating neuroinflammation and NLRP3-driven pathology.
  • Targeting FMR1 could be a novel strategy for treating multiple sclerosis.

More Related Videos

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages06:52

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages

Published on: May 21, 2018

11.3K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.9K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
12.0K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

3.5K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
6.7K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.1K