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ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death

Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the pa...

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Autores principales: Liu, Zhengzhao, Li, Hongming, Hong, Chungu, Chen, Menglu, Yue, Tao, Chen, Chunyuan, Wang, Zhenxing, You, Qing, Li, Chuanyin, Weng, Qinjie, Xie, Hui, Hu, Ronggui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251386/
https://www.ncbi.nlm.nih.gov/pubmed/30519240
http://dx.doi.org/10.3389/fimmu.2018.02647
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author Liu, Zhengzhao
Li, Hongming
Hong, Chungu
Chen, Menglu
Yue, Tao
Chen, Chunyuan
Wang, Zhenxing
You, Qing
Li, Chuanyin
Weng, Qinjie
Xie, Hui
Hu, Ronggui
author_facet Liu, Zhengzhao
Li, Hongming
Hong, Chungu
Chen, Menglu
Yue, Tao
Chen, Chunyuan
Wang, Zhenxing
You, Qing
Li, Chuanyin
Weng, Qinjie
Xie, Hui
Hu, Ronggui
author_sort Liu, Zhengzhao
collection PubMed
description Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the patients, with the underlying mechanisms incompletely understood yet. Mutations in human Optn (Optineurin), particularly E478G, have been found in many ALS patients. In this work, we report that NF-κB activity was increased in Optn knockout (Optn(−/−)) MEF (mouse embryonic fibroblast) cells expressing OPTN of different ALS-associated mutants especially E478G. Inflammation was significantly activated in mice infected with lenti-virus that allowed overexpression of OPTN(E478G) mutation in the motor cortex, with marked increase in the secretion of pro-inflammatory cytokines as well as neuronal cell death. Our work with both cell and animal models strongly suggested that anti-inflammation treatment could represent a powerful strategy to intervene into disease progression in ALS patients who possess the distinctive mutations in OPTN gene.
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spelling pubmed-62513862018-12-05 ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death Liu, Zhengzhao Li, Hongming Hong, Chungu Chen, Menglu Yue, Tao Chen, Chunyuan Wang, Zhenxing You, Qing Li, Chuanyin Weng, Qinjie Xie, Hui Hu, Ronggui Front Immunol Immunology Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the patients, with the underlying mechanisms incompletely understood yet. Mutations in human Optn (Optineurin), particularly E478G, have been found in many ALS patients. In this work, we report that NF-κB activity was increased in Optn knockout (Optn(−/−)) MEF (mouse embryonic fibroblast) cells expressing OPTN of different ALS-associated mutants especially E478G. Inflammation was significantly activated in mice infected with lenti-virus that allowed overexpression of OPTN(E478G) mutation in the motor cortex, with marked increase in the secretion of pro-inflammatory cytokines as well as neuronal cell death. Our work with both cell and animal models strongly suggested that anti-inflammation treatment could represent a powerful strategy to intervene into disease progression in ALS patients who possess the distinctive mutations in OPTN gene. Frontiers Media S.A. 2018-11-14 /pmc/articles/PMC6251386/ /pubmed/30519240 http://dx.doi.org/10.3389/fimmu.2018.02647 Text en Copyright © 2018 Liu, Li, Hong, Chen, Yue, Chen, Wang, You, Li, Weng, Xie and Hu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Liu, Zhengzhao
Li, Hongming
Hong, Chungu
Chen, Menglu
Yue, Tao
Chen, Chunyuan
Wang, Zhenxing
You, Qing
Li, Chuanyin
Weng, Qinjie
Xie, Hui
Hu, Ronggui
ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death
title ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death
title_full ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death
title_fullStr ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death
title_full_unstemmed ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death
title_short ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death
title_sort als-associated e478g mutation in human optn (optineurin) promotes inflammation and induces neuronal cell death
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251386/
https://www.ncbi.nlm.nih.gov/pubmed/30519240
http://dx.doi.org/10.3389/fimmu.2018.02647
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