title: Immunoproteasome in cancer and neuropathologies: a new therapeutic target?
abstract: Immunoproteasome is an emerging biological target that constitutes a key element not only in antigen presentation but also in T cell and cytokine regulation as well as cellular homeostasis. Respect to standard proteasome, the inducible expression and different sensitivity towards activity modulators of immunoproteasome render it a potential therapeutic target for tumours and central nervous system diseases. In this review we report the cutting edge studies for understanding when immunoproteasome expression is induced and how it regulates pivotal pathways involved in tumours and neuropathologies, including apoptosis and inflammation. We emphasize its role as a new pharmacological target by describing the recent medicinal chemistry efforts aimed at design selective small-molecule modulators of both standard- and immuno-proteasome forms. Finally, we also present an in silico model of the human immunoproteasome structure by the major molecular differences with the 20S standard proteasome and discuss the perspective for the design of novel specific smallmolecule modulators for the different proteasome isoforms.
authors.affiliation: Department of Experimental Pathology, University of Bologna, via S. Giacomo 12, 40126 Bologna, Italy. elena.bellavista2@unibo.it
authors.forename: Elena
authors.initials: E
authors.lastname: Bellavista
authors.forename: Federico
authors.initials: F
authors.lastname: Andreoli
authors.forename: Marco Daniele
authors.initials: MD
authors.lastname: Parenti
authors.forename: Morena
authors.initials: M
authors.lastname: Martucci
authors.forename: Aurelia
authors.initials: A
authors.lastname: Santoro
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.forename: Agostino
authors.initials: A
authors.lastname: Baruzzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Rio
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology; D003198:Computer Simulation; D016207:Cytokines / Q000276:immunology; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D020033:Protein Isoforms; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D020033:Protein Isoforms; D046988:Proteasome Endopeptidase Complex