title: Current understanding on the role of standard and immunoproteasomes in inflammatory/immunological pathways of multiple sclerosis.
abstract: The ubiquitin-proteasome system is the major intracellular molecular machinery for protein degradation and maintenance of protein homeostasis in most human cells. As ubiquitin-proteasome system plays a critical role in the regulation of the immune system, it might also influence the development and progression of multiple sclerosis (MS). Both ex vivo analyses and animal models suggest that activity and composition of ubiquitin-proteasome system are altered in MS. Proteasome isoforms endowed of immunosubunits may affect the functionality of different cell types such as CD8(+) and CD4(+) T cells and B cells as well as neurons during MS development. Furthermore, the study of proteasome-related biomarkers, such as proteasome antibodies and circulating proteasomes, may represent a field of interest in MS. Proteasome inhibitors are already used as treatment for cancer and the recent development of inhibitors selective for immunoproteasome subunits may soon represent novel therapeutic approaches to the different forms of MS. In this review we describe the current knowledge on the potential role of proteasomes in MS and discuss the pro et contra of possible therapies for MS targeting proteasome isoforms.
authors: Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity "L. Galvani" (CIG), University of Bologna, 40126 Bologna, Italy ; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
authors: Elena
authors: E
authors: Bellavista
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
authors: Aurelia
authors: A
authors: Santoro
authors: Neurology Unit, Department of Pathophosiology and Transplantation, University of Milan, Centro Dino Ferrari, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
authors: Daniela
authors: D
authors: Galimberti
authors: Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, "Amedeo Avogadro," 28100 Novara, Italy.
authors: Cristoforo
authors: C
authors: Comi
authors: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors: Fabio
authors: F
authors: Luciani
authors: Institut für Biochemie, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany ; Centro Interdipartimentale di Ricerca sul Cancro "Giorgio Prodi," University of Bologna, 40126 Bologna, Italy.
authors: Michele
authors: M
authors: Mishto