The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. The recent studies have suggested that the protein abnormalities could play some important roles in ALS because several protein mutations were found in individuals with this disease. However, proteins that are currently known to be associated with ALS only explain the pathogenesis of this disease in a minority of cases, thus, further screening is needed to identify other ALS-related proteins. In this study, we systematically analyzed and compared the brain proteomic alterations between a mouse model of ALS, the Tg(SOD1*G93A)1Gur model, and wild-type mice using isobaric tags for relative and absolute quantitation (iTRAQ) as well as bioinformatics methods. The results revealed some significant up- and downregulated proteins at the different developmental stages in the ALS-like mice as well as the possibly related cellular components, molecular functions, biological processes, and pathways in the development of ALS. Our results identified some possible proteins that participate in the pathogenesis of ALS as well as the cellular components that are damaged by these proteins, we additionally identified the molecular functions, the biological processes, and the pathways of these proteins as well as the molecules that are associated with these pathways. This study represents an important preliminary investigation of the role of proteomic abnormalities in the pathogenesis of ALS, both in human patients and other animal models. We present some novel findings that may serve as a basis for further investigation of abnormal proteins that are involved in the pathogenesis of ALS.