scholarly journals Neuronal RNA‐binding protein dysfunction in multiple sclerosis cortex

2020 ◽  
Vol 7 (7) ◽  
pp. 1214-1224
Author(s):  
Hannah E. Salapa ◽  
Catherine Hutchinson ◽  
Bogdan F. Popescu ◽  
Michael C. Levin
Keyword(s):  
Multiple Sclerosis ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Dysfunction

scholarly journals The Potential Contribution of Dysfunctional RNA-Binding Proteins to the Pathogenesis of Neurodegeneration in Multiple Sclerosis and Relevant Models

2020 ◽  
Vol 21 (13) ◽  
pp. 4571 ◽  
Author(s):  
Cole D. Libner ◽  
Hannah E. Salapa ◽  
Michael C. Levin
Keyword(s):  
Multiple Sclerosis ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Potential Contribution ◽  
Novel Therapies ◽  
Permanent Disability ◽  
Central Nervous System Damage ◽  
Protein Dysfunction

Neurodegeneration in multiple sclerosis (MS) is believed to underlie disease progression and permanent disability. Many mechanisms of neurodegeneration in MS have been proposed, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, and RNA-binding protein dysfunction. The purpose of this review is to highlight mechanisms of neurodegeneration in MS and its models, with a focus on RNA-binding protein dysfunction. Studying RNA-binding protein dysfunction addresses a gap in our understanding of the pathogenesis of MS, which will allow for novel therapies to be generated to attenuate neurodegeneration before irreversible central nervous system damage occurs.

Unraveling a new player in multiple sclerosis pathogenesis: The RNA-binding protein HuR

2020 ◽  
Vol 41 ◽  
pp. 102048 ◽  
Author(s):  
Cristiana Pistono ◽  
Maria Cristina Monti ◽  
Nicoletta Marchesi ◽  
Chiara Boiocchi ◽  
Lucrezia Irene Maria Campagnoli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Multiple Sclerosis Pathogenesis

scholarly journals Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis

2020 ◽  
Author(s):  
Vittoria Borgonetti ◽  
Maria Domenica Sanna ◽  
Laura Lucarini ◽  
Nicoletta Galeotti
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Rna Binding ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Rna Binding Protein ◽  
Motor Dysfunction ◽  
Autoimmune Encephalomyelitis ◽  
Activated Microglia ◽  
Experimental Autoimmune

AbstractMultiple 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.

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