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Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease

BACKGROUND: Neurodegeneration is believed to be the primary cause of permanent, long-term disability in patients with multiple sclerosis. The cause of neurodegeneration in multiple sclerosis appears to be multifactorial. One mechanism that has been implicated in the pathogenesis of neurodegeneration...

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Autores principales: Douglas, Joshua N., Gardner, Lidia A., Salapa, Hannah E., Lalor, Stephen J., Lee, Sangmin, Segal, Benjamin M., Sawchenko, Paul E., Levin, Michael C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938923/
https://www.ncbi.nlm.nih.gov/pubmed/27391474
http://dx.doi.org/10.1186/s12974-016-0647-y
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author Douglas, Joshua N.
Gardner, Lidia A.
Salapa, Hannah E.
Lalor, Stephen J.
Lee, Sangmin
Segal, Benjamin M.
Sawchenko, Paul E.
Levin, Michael C.
author_facet Douglas, Joshua N.
Gardner, Lidia A.
Salapa, Hannah E.
Lalor, Stephen J.
Lee, Sangmin
Segal, Benjamin M.
Sawchenko, Paul E.
Levin, Michael C.
author_sort Douglas, Joshua N.
collection PubMed
description BACKGROUND: Neurodegeneration is believed to be the primary cause of permanent, long-term disability in patients with multiple sclerosis. The cause of neurodegeneration in multiple sclerosis appears to be multifactorial. One mechanism that has been implicated in the pathogenesis of neurodegeneration in multiple sclerosis is the targeting of neuronal and axonal antigens by autoantibodies. Multiple sclerosis patients develop antibodies to the RNA-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which is enriched in neurons. We hypothesized that anti-hnRNP A1 antibodies would contribute to neurodegeneration in an animal model of multiple sclerosis. METHODS: Following induction of experimental autoimmune encephalomyelitis (EAE) by direct immunization with myelin oligodendrocyte glycoprotein, mice were injected with anti-hnRNP A1 or control antibodies. Animals were examined clinically, and the central nervous system (CNS) tissues were tested for neurodegeneration with Fluoro-Jade C, a marker of degenerating neural elements. RESULTS: Injection of anti-hnRNP A1 antibodies in mice with EAE worsened clinical disease, altered the clinical disease phenotype, and caused neurodegeneration preferentially in the ventral spinocerebellar tract and deep white matter of the cerebellum in the CNS. Neurodegeneration in mice injected with hnRNP A1-M9 antibodies compared to control groups was consistent with “dying back” axonal degeneration. CONCLUSIONS: These data suggest that antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in immune-mediated disease of the CNS.
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spelling pubmed-49389232016-07-10 Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease Douglas, Joshua N. Gardner, Lidia A. Salapa, Hannah E. Lalor, Stephen J. Lee, Sangmin Segal, Benjamin M. Sawchenko, Paul E. Levin, Michael C. J Neuroinflammation Research BACKGROUND: Neurodegeneration is believed to be the primary cause of permanent, long-term disability in patients with multiple sclerosis. The cause of neurodegeneration in multiple sclerosis appears to be multifactorial. One mechanism that has been implicated in the pathogenesis of neurodegeneration in multiple sclerosis is the targeting of neuronal and axonal antigens by autoantibodies. Multiple sclerosis patients develop antibodies to the RNA-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which is enriched in neurons. We hypothesized that anti-hnRNP A1 antibodies would contribute to neurodegeneration in an animal model of multiple sclerosis. METHODS: Following induction of experimental autoimmune encephalomyelitis (EAE) by direct immunization with myelin oligodendrocyte glycoprotein, mice were injected with anti-hnRNP A1 or control antibodies. Animals were examined clinically, and the central nervous system (CNS) tissues were tested for neurodegeneration with Fluoro-Jade C, a marker of degenerating neural elements. RESULTS: Injection of anti-hnRNP A1 antibodies in mice with EAE worsened clinical disease, altered the clinical disease phenotype, and caused neurodegeneration preferentially in the ventral spinocerebellar tract and deep white matter of the cerebellum in the CNS. Neurodegeneration in mice injected with hnRNP A1-M9 antibodies compared to control groups was consistent with “dying back” axonal degeneration. CONCLUSIONS: These data suggest that antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in immune-mediated disease of the CNS. BioMed Central 2016-07-08 /pmc/articles/PMC4938923/ /pubmed/27391474 http://dx.doi.org/10.1186/s12974-016-0647-y Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Douglas, Joshua N.
Gardner, Lidia A.
Salapa, Hannah E.
Lalor, Stephen J.
Lee, Sangmin
Segal, Benjamin M.
Sawchenko, Paul E.
Levin, Michael C.
Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease
title Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease
title_full Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease
title_fullStr Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease
title_full_unstemmed Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease
title_short Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease
title_sort antibodies to the rna-binding protein hnrnp a1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938923/
https://www.ncbi.nlm.nih.gov/pubmed/27391474
http://dx.doi.org/10.1186/s12974-016-0647-y
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