Proteasome inhibitors as experimental therapeutics of autoimmune diseases

Current treatment strategies for rheumatoid arthritis (RA) consisting of disease-modifying anti-rheumatic drugs or biological agents are not always effective, hence driving the demand for new experimental therapeutics. The antiproliferative capacity of proteasome inhibitors (PIs) has received consid...

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Vydáno v:	Arthritis research & therapy Ročník 17; číslo 1; s. 17
Hlavní autoři:	Verbrugge, Sue Ellen, Scheper, Rik J, Lems, Willem F, de Gruijl, Tanja D, Jansen, Gerrit
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 28.01.2015 BioMed Central Ltd
Témata:	Antigen presenting cells Antigens Antirheumatic agents Arthritis, Rheumatoid - drug therapy Autoimmune Diseases - drug therapy Development and progression Drug therapy Health aspects Homeopathy Humans Interleukins Materia medica and therapeutics Medicine Medicine & Public Health Orthopedics Physiological aspects Proteasome Endopeptidase Complex - adverse effects Proteasome Inhibitors - therapeutic use Review Rheumatoid factor Rheumatology Systemic lupus erythematosus T cells Therapeutics Systemic Lupus Erythematosus Major Histocompatibility Complex Class Immune Effector Cell Bortezomib Rheumatoid Arthritis
ISSN:	1478-6354, 1478-6362, 1478-6354, 1478-6362
On-line přístup:	Získat plný text
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Popis
Shrnutí:	Current treatment strategies for rheumatoid arthritis (RA) consisting of disease-modifying anti-rheumatic drugs or biological agents are not always effective, hence driving the demand for new experimental therapeutics. The antiproliferative capacity of proteasome inhibitors (PIs) has received considerable attention given the success of their first prototypical representative, bortezomib (BTZ), in the treatment of B cell and plasma cell-related hematological malignancies. Therapeutic application of PIs in an autoimmune disease setting is much less explored, despite a clear rationale of (immuno) proteasome involvement in (auto)antigen presentation, and PIs harboring the capacity to inhibit the activation of nuclear factor-κB and suppress the release of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. Here, we review the clinical positioning of (immuno) proteasomes in autoimmune diseases, in particular RA, systemic lupus erythematosus, Sjögren’s syndrome and sclerodema, and elaborate on (pre)clinical data related to the impact of BTZ and next generation PIs on immune effector cells (T cells, B cells, dendritic cells, macrophages, osteoclasts) implicated in their pathophysiology. Finally, factors influencing long-term efficacy of PIs, their current (pre)clinical status and future perspectives as anti-inflammatory and anti-arthritic agents are discussed.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	1478-6354 1478-6362 1478-6354 1478-6362
DOI:	10.1186/s13075-015-0529-1