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Critical Reviews™ in Immunology
Factor de Impacto: 1.352 Factor de Impacto de 5 años: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v26.i6.20
pages 487-498

The Proteasome and Its Inhibitors in Immune Regulation and Immune Disorders

Alessio Nencioni
Department of Internal Medicine, University of Genova, 16132 Genova, Italy; and Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Frank Grunebach
Department of Hematology, Oncology and Immunology, University of Tübingen, D-72076 Tübingen, Germany
Franco Patrone
Department of Internal Medicine, University of Genova, 16132 Genova, Italy
Alberto Ballestrero
Department of Internal Medicine, University of Genova, 16132 Genova, Italy
Peter Brossart
Department of Hematology, Oncology and Immunology, University of Tübingen, Otfried Muller Str. 10; D-72076 Tübingen, Germany


The ubiquitin-proteasome pathway is a well-characterized mechanism deputed to the degradation of intracellular proteins. Proteasomal degradation intervenes in the regulation of numerous cellular functions including signal transduction, apoptosis, cell cycle, and antigen presentation. In vitro and in vivo studies have shown that both normal and malignant cells of the immune system are exquisitely affected by inhibition of proteasome activity. This property is currently exploited in the treatment of multiple myeloma and mantle cell lymphoma, two B-cell malignancies that respond to treatment with the proteasome inhibitor bortezomib. Pharmacological inhibitors of the proteasome also affect function and survival of B and T lymphocytes and of dendritic cells and were shown to reduce autoimmune and inflammatory manifestations in several models of immune-mediated disorders. The present review offers an overview of the mechanisms implicated in the immunomodulatory effects of proteasome inhibitors and discusses prospective future applications for these small molecules in immune and inflammatory diseases.

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