Related Experiment Video
Updated: Nov 30, 2025
Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis:
Vittoria Borgonetti1, Maria Domenica Sanna1, Laura Lucarini1
1Section of Pharmacology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.
Abstract:
Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalomyelitis (EAE) in mice, by focusing on HuR, an RNA-binding protein involved in inflammatory and immune phenomena. Spinal cord sections of EAE mice showed an increased HuR immunostaining that was abundantly detected in the cytoplasm of activated microglia, a pattern associated with its increased activity. Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) decreased the proinflammatory activated microglia, inflammatory infiltrates, and the expression of the proinflammatory cytokines IL-1β, TNF-α, and IL-17, and inhibited the activation of the NF-κB pathway. The beneficial effect of anti-HuR ASO in EAE mice corresponded also to a decreased permeability of the blood-brain barrier. EAE mice showed a reduced spinal CD206 immunostaining that was restored by anti-HuR ASO, indicating that HuR silencing promotes a shift to the anti-inflammatory and regenerative microglia phenotype. Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss. Targeting HuR might represent an innovative and promising perspective to control neurological disturbances in MS patients.
Insights
Targeting HuR, an RNA-binding protein, reduced neuroinflammation and improved motor function in experimental autoimmune encephalomyelitis (EAE) mice. This suggests HuR is a potential therapeutic target for multiple sclerosis (MS) treatment.
Area of Science:
- Neuroimmunology
- Molecular Biology
- RNA Biology
Background:
- Multiple sclerosis (MS) is a chronic CNS autoimmune disease involving neuroinflammation and demyelination.
- Activated microglia contribute to neuroinflammation and neuronal damage in MS pathogenesis.
- Post-transcriptional regulation, specifically by RNA-binding proteins like HuR, plays a role in inflammatory processes.
Purpose of the Study:
- To investigate the role of HuR in neuroinflammation during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
- To assess the therapeutic potential of targeting HuR in EAE.
Main Methods:
- Spinal cord sections from EAE mice were analyzed for HuR expression.
- Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) was used to inhibit HuR.
- Evaluated microglial activation, inflammatory infiltrates, cytokine expression (IL-1β, TNF-α, IL-17), NF-κB pathway activation, blood-brain barrier permeability, and CD206 expression.
- Assessed motor function, pain, and body weight changes in treated EAE mice.
Main Results:
- Increased HuR expression and cytoplasmic localization were observed in activated microglia in EAE spinal cords.
- Anti-HuR ASO treatment reduced activated microglia, inflammatory infiltrates, and pro-inflammatory cytokine levels.
- HuR inhibition decreased NF-κB pathway activation, blood-brain barrier permeability, and promoted a shift towards an anti-inflammatory microglia phenotype (restored CD206 expression).
- Anti-HuR ASO treatment improved motor deficits, pain hypersensitivity, and body weight loss in EAE mice.
Conclusions:
- HuR is upregulated in activated microglia during EAE and contributes to neuroinflammation.
- Targeting HuR with an antisense oligonucleotide ameliorates EAE pathology and neurological symptoms.
- HuR represents a promising therapeutic target for managing neuroinflammation and neurological dysfunction in MS.
