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Proteasome inhibition: a new anti-inflammatory strategy

Elliott, Peter J.
Zollner, Thomas Matthias
Published in Journal of Molecular Medicine. 2003, vol. 81, no. 4, p. 235-245
Abstract The ubiquitin-proteasome pathway has a central role in the selective degradation of intracellular proteins. Among the key proteins modulated by the proteasome are those involved in the control of inflammatory processes, cell cycle regulation, and gene expression. Consequently proteasome inhibition is a potential treatment option for cancer and inflammatory conditions. Thus far, proof of principle has been obtained from studies in numerous animal models for a variety of human diseases including cancer, reperfusion injury, and inflammatory conditions such as rheumatoid arthritis, asthma, multiple sclerosis, and psoriasis. Two proteasome inhibitors, each representing a unique chemical class, are currently under clinical evaluation. Velcade (PS-341) is currently being evaluated in multiple phase II clinical trials for several solid tumor indications and has just entered a phase III trial for multiple myeloma. PS-519, representing another class of inhibitors, focuses on the inflammatory events following ischemia and reperfusion injury. Since proteasome inhibitors exhibit anti-inflammatory and antiproliferative effects, diseases characterized by both of these processes simultaneously, as is the case in rheumatoid arthritis or psoriasis, might also represent clinical opportunities for such drugs.
Keywords Acetylcysteine/*analogs & derivatives/therapeutic useAnimalsAnti-Inflammatory Agents/*therapeutic useAntineoplastic Agents/therapeutic useArthritis, Rheumatoid/drug therapyAsthma/drug therapyBoronic Acids/therapeutic useClinical Trials as TopicCysteine EndopeptidasesDisease Models, AnimalHumansInflammation/drug therapyLysine/chemistryModels, BiologicalModels, ChemicalMultienzyme Complexes/*antagonists & inhibitorsMultiple Sclerosis/drug therapyNF-kappa B/metabolismNeoplasms/drug therapyPeptides/chemistryProtease Inhibitors/therapeutic useProteasome Endopeptidase ComplexPsoriasis/drug therapyPyrazines/therapeutic useReperfusion Injury
PMID: 12700891
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ELLIOTT, Peter J., ZOLLNER, Thomas Matthias, BOEHNCKE, Wolf-Henning. Proteasome inhibition: a new anti-inflammatory strategy. In: Journal of Molecular Medicine, 2003, vol. 81, n° 4, p. 235-245. doi: 10.1007/s00109-003-0422-2

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Deposited on : 2013-09-20

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