A Bioinformatic Investigation of Proteasome And Autophagy Expression in The Central Nervous System

Abstract: The ubiquitin proteasome system (UPS) and autophagy lysosome pathway (ALP) play major roles in protein quality control. However, data regarding the relative significance of UPS and ALP in the central nervous system (CNS) remain limited. In this study, we reckon the quantitative expression status of UPS- and ALP-related genes and their products in the CNS compared to that in other tissues. We collected human and mouse gene expression datasets from the reference expression dataset (RefEx) and Genevestigator (a tool for handling curated transcriptomic data from public repositories) and human proteomics data from the proteomics database (ProteomicsDB). The expression levels of genes and proteins in four categories—ubiquitin, proteasome, autophagy, and lysosome in cells and tissues were extracted. Perturbation of expression by drugs was also analyzed based on the four categories. Compared to that for the other three categories, proteasome gene expression was consistently low in the CNS of mice, and was more pronounced in humans. Neural stem cells and neurons showed low proteasome gene expressions when compared to non-neuronal stem cells. Proteomic analyses, however, did not show trends similar to those observed in the gene expression analyses. Perturbation analyses revealed that agents such as azithromycin and vitamin D3 upregulated the expression of both the UPS and ALP. Disproportional expression of the UPS and ALP might play a role in the pathophysiology of CNS disorders and this imbalance might be redressed by several therapeutic candidates.