Targeting immunoproteasome in neurodegeneration: A glance to the future

The immunoproteasome is a specialized form of proteasome equipped with modified catalytic subunits that was initially discovered to play a pivotal role in MHC class I antigen processing and immune system modulation. How-ever, over the last years, this proteolytic complex has been uncovered to serve additional functions unrelated to antigen presentation. Accordingly, it has been proposed that immunoproteasome synergizes with canonical pro-teasome in different cell types of the nervous system, regulating neurotransmission, metabolic pathways and adaptation of the cells to redox or inflammatory insults. Hence, studying the alterations of immunoproteasome expression and activity is gaining research interest to define the dynamics of neuroinflammation as well as the early and late molecular events that are likely involved in the pathogenesis of a variety of neurological disorders. Furthermore, these novel functions foster the perspective of immunoproteasome as a potential therapeutic target for neurodegeneration. In this review, we provide a brain and retina-wide overview, trying to correlate present knowledge on structure-function relationships of immunoproteasome with the variety of observed neuro-modulatory functions.(c) 2022 Published by Elsevier Inc.

Automated summary

The immunoproteasome, initially discovered for its role in MHC class I antigen processing and immune system modulation, has been found to have additional functions unrelated to antigen presentation. Its expression and activity alterations are important in understanding neuroinflammation dynamics and the pathogenesis of neurological disorders. Furthermore, these new functions suggest the potential of immunoproteasome as a therapeutic target for neurodegeneration. This review provides an overview of the structure-function relationships of immunoproteasome and its observed neuro-modulatory functions.