Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a significant neurodegenerative component. Dysfunctional RNA-binding proteins (RBPs) are causally linked to neuronal damage and are a feature of MS, including the mislocalization of the RBP heterogeneous nuclear ri...

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Main Authors: Muxue Li, Rachel Hamilton, Hannah E. Salapa, Michael C. Levin
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/11/10/1282
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author Muxue Li
Rachel Hamilton
Hannah E. Salapa
Michael C. Levin
author_facet Muxue Li
Rachel Hamilton
Hannah E. Salapa
Michael C. Levin
author_sort Muxue Li
collection DOAJ
description Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a significant neurodegenerative component. Dysfunctional RNA-binding proteins (RBPs) are causally linked to neuronal damage and are a feature of MS, including the mislocalization of the RBP heterogeneous nuclear ribonucleoprotein A1 (A1). Here, we show that primary neurons exposed to pro-inflammatory cytokines and anti-A1 antibodies, both characteristic of an MS autoimmune response, displayed increased A1 mislocalization, stress granule formation, and decreased neurite length, a marker of neurodegeneration. These findings illustrate a significant relationship between secreted immune factors, A1 dysfunction, and neuronal damage in a disease-relevant model system.
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spelling doaj.art-bb6ab4cbc93e42e39f9571cb10dc55552023-11-22T17:36:46ZengMDPI AGBrain Sciences2076-34252021-09-011110128210.3390/brainsci11101282Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical NeuronsMuxue Li0Rachel Hamilton1Hannah E. Salapa2Michael C. Levin3Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaDepartment of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaOffice of the Saskatchewan Multiple Sclerosis Clinical Research Chair, University of Saskatchewan, Saskatoon, SK S7N 0M7, CanadaDepartment of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaMultiple sclerosis (MS) is an inflammatory disease of the central nervous system with a significant neurodegenerative component. Dysfunctional RNA-binding proteins (RBPs) are causally linked to neuronal damage and are a feature of MS, including the mislocalization of the RBP heterogeneous nuclear ribonucleoprotein A1 (A1). Here, we show that primary neurons exposed to pro-inflammatory cytokines and anti-A1 antibodies, both characteristic of an MS autoimmune response, displayed increased A1 mislocalization, stress granule formation, and decreased neurite length, a marker of neurodegeneration. These findings illustrate a significant relationship between secreted immune factors, A1 dysfunction, and neuronal damage in a disease-relevant model system.https://www.mdpi.com/2076-3425/11/10/1282RNA-binding proteinmultiple sclerosisstress granulesheterogeneous nuclear ribonucleoprotein A1cytokinesautoimmunity
spellingShingle Muxue Li
Rachel Hamilton
Hannah E. Salapa
Michael C. Levin
Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons
Brain Sciences
RNA-binding protein
multiple sclerosis
stress granules
heterogeneous nuclear ribonucleoprotein A1
cytokines
autoimmunity
title Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons
title_full Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons
title_fullStr Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons
title_full_unstemmed Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons
title_short Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons
title_sort pro inflammatory cytokines and antibodies induce hnrnp a1 dysfunction in mouse primary cortical neurons
topic RNA-binding protein
multiple sclerosis
stress granules
heterogeneous nuclear ribonucleoprotein A1
cytokines
autoimmunity
url https://www.mdpi.com/2076-3425/11/10/1282
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AT rachelhamilton proinflammatorycytokinesandantibodiesinducehnrnpa1dysfunctioninmouseprimarycorticalneurons
AT hannahesalapa proinflammatorycytokinesandantibodiesinducehnrnpa1dysfunctioninmouseprimarycorticalneurons
AT michaelclevin proinflammatorycytokinesandantibodiesinducehnrnpa1dysfunctioninmouseprimarycorticalneurons