Journal
CELLS
Volume 10, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cells10081929
Keywords
immunoproteasome; inhibition; inflammation; autoimmune diseases; drug development
Categories
Funding
- German Research Foundation (DFG) [1861/10-3]
- Young Scholars' Program of the Bavarian Academy of Sciences and Humanities
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The review highlights the significance of immunoproteasome (iCP) inhibitors in scientific and medicinal applications, showcasing their potential in treating autoimmune diseases and chronic inflammations.
At the heart of the ubiquitin-proteasome system, the 20S proteasome core particle (CP) breaks down the majority of intracellular proteins tagged for destruction. Thereby, the CP controls many cellular processes including cell cycle progression and cell signalling. Inhibitors of the CP can suppress these essential biological pathways, resulting in cytotoxicity, an effect that is beneficial for the treatment of certain blood cancer patients. During the last decade, several preclinical studies demonstrated that selective inhibition of the immunoproteasome (iCP), one of several CP variants in mammals, suppresses autoimmune diseases without inducing toxic side effects. These promising findings led to the identification of natural and synthetic iCP inhibitors with distinct chemical structures, varying potency and subunit selectivity. This review presents the most prominent iCP inhibitors with respect to possible scientific and medicinal applications, and discloses recent trends towards pan-immunoproteasome reactive inhibitors that cumulated in phase II clinical trials of the lead compound KZR-616 for chronic inflammations.
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