Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

For Online Access

Best Paper Award Selection - Editorial Board Site

2006, Volume26

Issue 6

111 pages

Issue price - $142.00

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, M.D.
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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