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Proteomics analysis indicates the involvement of immunity and inflammation in the onset stage of SOD1-G93A mouse model of ALS

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机构: [1]Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, China [2]Beijing Geriatric Healthcare Center, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China [3]Xiangya School of Medicine, Central South University, No.172 Tongzipo Road, Changsha, Hunan 410013, China [4]Department of Geriatrics, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, China [5]Beijing Municipal Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China
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关键词: Amyotrophic lateral sclerosis 4D label-free quantitative proteomics Parallel reaction monitoring Immunity and inflammation SOD1-G93A mouse Lumbar spinal cord

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Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease, and the pathogenic mechanism that underlies ALS is still unclear. We analyzed the differentially expressed proteins (DEPs) in the spinal cord between SOD1-G93A transgenic mice at the onset stage and non-transgenic (NTG) littermates based on 4D label-free quantitative proteomics (4D-LFQ) with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, 189 DEPs were screened, of which 166 were up-regulated and 23 down-regulated. Clusters of Orthologous Groups (COG)/ EuKaryotic Orthologous Groups (KOG) classification, subcellular localization annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, clustering analysis and protein-protein interaction (PPI) network analyses were performed. Parallel reaction monitoring (PRM) analysis validated 48 proteins from immunity and inflammation-related pathways of KEGG. We described the function and distribution of DEPs, most of which were involved in the following pathways: complement and coagulation cascades, antigen processing and presentation, NF-kappa B signaling pathway, Retinoic acid-inducible gene I (RIG) -I-like receptor signaling pathway, the extracellular matrix-receptor (ECM-receptor) interaction, focal adhesion, phagosome and lysosome. PPI network analysis identified Fn1, Fga, Serpina1e and Serpina3n as potential biomarkers. Our discoveries broaden the view and expand our understanding of immunity and inflammation in ALS. SIGNIFICANCE: This study gives a comprehensive description of DEPs in the spinal cord proteomics of SOD1-G93A mice at the onset period. Compared with a previous study focusing on progressive stage, we showed that immunity and inflammation play an important role at the onset stage of ALS. Several pathways validated by PRM bring new insight to the pathological mechanisms of ALS. The participation of RIG-I-like signaling pathway in ALS and potential biomarkers Fga, Fn1, Serpina1e and Serpina3n are supplements to existing knowledge.Copyright © 2022. Published by Elsevier B.V.

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 2 区 生化研究方法
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大类 | 3 区 生物学
小类 | 2 区 生化研究方法
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Q2 BIOCHEMICAL RESEARCH METHODS
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Q2 BIOCHEMICAL RESEARCH METHODS

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第一作者机构: [1]Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, China [2]Beijing Geriatric Healthcare Center, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China
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通讯机构: [2]Beijing Geriatric Healthcare Center, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China [5]Beijing Municipal Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China [*1]Beijing Geriatric Healthcare Center, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng, Beijing 100053,China
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