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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MDPI AG
2021-09-01
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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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issn | 2076-3425 |
language | English |
last_indexed | 2024-03-10T06:41:46Z |
publishDate | 2021-09-01 |
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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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