Targeting immunoproteasome in neurodegeneration: A glance to the future

  • Pharmacol Ther. 2023 Jan:241:108329. doi: 10.1016/j.pharmthera.2022.108329.
Grazia R Tundo  1 ,  Paolo Cascio  2 ,  Danilo Milardi  3 ,  Anna Maria Santoro  3 ,  Grazia Graziani  4 ,  Pedro Miguel Lacal  5 ,  Alessio Bocedi  6 ,  Francesco Oddone  7 ,  Mariacristina Parravano  7 ,  Andrea Coletta  8 ,  Massimo Coletta  7 ,  Diego Sbardella  9
Affiliations
  • 1. Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy. Electronic address: [email protected].
  • 2. Department of Veterinary Sciences, University of Turin, Largo P. Braccini 2, 100095 Grugliasco, Italy.
  • 3. Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Via P. Gaifami 18, 95126 Catania, Italy.
  • 4. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
  • 5. Laboratory of Molecular Oncology, IDI-IRCCS, Rome, Italy.
  • 6. Department of Chemical Sciences and Technologies, University of Rome 'Tor Vergata', Via della Ricerca Scientifica 1, 00133 Rome, Italy.
  • 7. IRCCS Fondazione Bietti, Rome, Italy.
  • 8. Claviate, Aarhus, Denmark.
  • 9. IRCCS Fondazione Bietti, Rome, Italy. Electronic address: [email protected].
PMID: 36526014 DOI: 10.1016/j.pharmthera.2022.108329
Abstract

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. However, 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 Proteasome 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.

Keywords
Immunoproteasome; Neurodegeneration; PA28; Pharmacology; Retina.