Proteomics Analyses for the Global Proteins in the Brain Tissues of Different Human Prion Diseases*

Abstract

Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases.

Plasma-based proteomics reveals immune response, complement and coagulation cascades pathway shifts in heat-stressed lactating dairy cows

“…change (the proteins with 1.2-fold changes relative to the normal control were based on the published reference [15,16]) with a Q-value less than 0.05, and 2) the third ratio was more than 1.0-fold change with a Q-value less than 0.05.…”

Quantitative Proteomic Analysis Reveals Similarities between Huntington’s Disease (HD) and Huntington’s Disease-Like 2 (HDL2) Human Brains

“…18 Previous proteomics studies of HD include the analysis of Htt protein interactome in mouse and cell models 19–21 and mouse brain proteomics studies. 22–24 These analyses identified a number of cellular processes and pathways affected in HD, including energy production and metabolism, gene transcription, protein translation, RNA processing, cytoskeleton dynamic, and protein trafficking.…”

Proteomics Approach to Identify Biomarkers in Neurodegenerative Diseases

“…The approach used was utilization of isobaric peptide tags (iTRAQ) and multidimensional LC-MS/MS to identify and differentiate proteins between prion disease affected and normal brain samples. Some of the upregulated proteins observed in the cortex and cerebellum of the patients, when compared to normal brains, were those involved in the metabolism, protein transport, development of nervous system symptoms such as ataxia, and reorganization of neuronal actin structure (Shi et al, 2015; Table 1). Some of the downregulated proteins include those involved in the actin cytoskeleton assembly and retrograde transport from early and late endosomes to the trans-Golgi network (Shi et al, 2015).…”

“…Some of the upregulated proteins observed in the cortex and cerebellum of the patients, when compared to normal brains, were those involved in the metabolism, protein transport, development of nervous system symptoms such as ataxia, and reorganization of neuronal actin structure (Shi et al, 2015; Table 1). Some of the downregulated proteins include those involved in the actin cytoskeleton assembly and retrograde transport from early and late endosomes to the trans-Golgi network (Shi et al, 2015). Animal studies have shown that prion disease-regulated genes could be found in gene families associated with lysosome organization/biogenesis, immune cell activation/inflammatory response, lipid metabolism, apoptosis, protein biosynthesis/proteolysis, nervous system function/synaptic transmission, and cytoskeleton organization/biogenesis (Rubenstein, 2012).…”

“…Although the accumulation of PrP Sc is the main causative factor in all prion diseases, it has been observed that several other brain proteins involved in vital biological processes and pathways also exhibit changes that might be contributing to the pathogenesis of prion diseases (Shi et al, 2015). Recently, brain samples from cortex and cerebellum were studied from individuals affected with different prion diseases (genetic CJD, sporadic CJD, and FFI) from a proteomics perspective.…”