Impact of immunoproteasome impairment on microglia cell function

The ubiquitin-proteasome system maintains the functional proteome of the cells by the clearance of damaged, misfolded, old and/or unneeded proteins. This is particularly important in the brain where protein accumulation has a hallmark of many neurodegenerative diseases that drives neuroinflammation. Microglia are the resident immune cells of the central nervous system and play a major role in the regulation of brain homeostasis via constitutive expression of standard proteasomes and immunoproteasomes (IP). Nevertheless, the impact of IP function on the innate immunity of CNS is not well described. Here, we analyzed ubiquitylated proteins in IP deficient microglia upon enrichment and under different conditions to identify the proteins preferentially degraded by the IP and to investigate the impact of the accumulation of these proteins on microglia function.