Preliminary Observation about Alteration of Proteins and Their Potential Functions in Spinal Cord of SOD1 G93A Transgenic Mice

Abstract

The protein abnormality participates in the development of ALS that meets with the widespread approval from major researchers. However, these currently found abnormal proteins aren't far enough to explain all pathogenesis of ALS. Therefore, the search of novel abnormal proteins participated in the pathogenesis of ALS is very necessary. In this study, we screened, compared and analyzed the differentially expressed proteins in the spinal cord of the SOD1 G93A transgenic and wild-type (WT) mice applying the isobaric tags for relative and absolute quantitation (iTRAQ) and the bioinformatics methods. The results revealed the details of significantly differentially expressed proteins between the SOD1 G93A transgenic and WT mice, and the damaged and/or regulated cellular components, molecular functions and biological processes and the significant enrichment pathways of these proteins. Our study comprehensively described the details of the possible abnormal proteins participated in the pathogenesis of SOD1 G93A transgenic mice, extensively explored their possible molecular mechanisms how to play the role in the development in this animal model, and provided some evidences and clues for further and deeply studying the relationship between the abnormal proteins and the pathogenesis of ALS in the other animal models and ALS patients.

The Chinese Medicinal Formulation Guzhi Zengsheng Zhitongwan Modulates Chondrocyte Structure, Dynamics, and Metabolism by Controlling Multiple Functional Proteins

“…The labeled peptide mixtures from the two groups were then equally mixed and dried using a speed-vacuum centrifuge (Thermo, USA). The dried labeled peptides were dissolved in 4 mL of strong cation exchange (SCX) buffer (25 mM NaH 2 PO 4 in 25% acetonitrile, pH 2.7) and fractionated using an Ultremex strong cation exchange column (Phenomenex, USA) on the LC-20AB high-performance liquid chromatography platform (Shimadzu, Japan) [9].…”

Identification of Molecular Correlations Between DHRS4 and Progressive Neurodegeneration in Amyotrophic Lateral Sclerosis By Gene Co-Expression Network Analysis

“…Thus, we selected the candidate hub genes from key modules. In addition, in our previous study, the isobaric tags for relative and absolute quantitation (iTRAQ) were applied to perform proteomic analysis on the spinal cord between SOD1 G93A mice and WT mice at 130 days of age ( 31 ). To screen stable and robust hub genes accurately, the selection of hub gene criteria is as follows: first of all, these genes were included in the key modules, with module membership >0.8 and gene significance >0.4; next, the genes presented in the progression stage of iTRAQ were upregulated; moreover, they are DEGs between WT mice and SOD1 G93A mice.…”

“…SOD1 G93A transgenic mice are the most classical and widely used animal model in ALS research, with a survival period of approximately 4–5 months, mostly showing symptoms of progressive muscle weakness and atrophy at 90–120 days of age, which progressively worsen ( 23 , 33 , 34 ). As mentioned earlier in the text, in our previous study, protein quantification and differential analysis of the spinal cord of SOD1 G93A mice in the symptomatic stage (130 days of age) were performed by the iTRAQ, but the temporal relationship between the differential proteins and disease progression was not clarified ( 31 ). To clarify proteins closely related to the progression of ALS, in this study, WGCNA was used to identify and validate that Dhrs4 expression in the spinal cord was upregulated with the progression of SOD1 G93A mice.…”

Potential proteomic alteration in the brain of Tg(SOD1*G93A)1Gur mice: A new pathogenesis insight of amyotrophic lateral sclerosis

“…html) for this purpose. The pathway analysis of differently expressed proteins indicated several significantly enriched pathways, including the autophagy‐related pathways (ribosome, phagosome, and lysosome), the inflammatory pathways (pathogenic Escherichia coli , staphylococcus aureus , and amebiasis), the autoimmune pathways (systemic lupus erythematosus, rheumatoid arthritis, and leukocyte transendothelial migration) and the pathways associated with the adherens junction, Wnt signaling, the amino sugar and nucleotide sugar metabolism, and the synaptic vesicle cycle (Table 4) (Cairns et al, 2004; Zhang et al, 2018) (http://www.genome.jp/kegg/ pathway. html).…”