Ubiquitin- and proteasome-dependent pathway of protein degradation as an emerging therapeutic target

The majority of cellular proteins are degraded by the ubiquitin-and proteasome-dependent proteolytic pathway. Among those proteins are various regulators of crucial processes, like the cell cycle, apoptosis, gene expression, angiogenesis, antigen presentation, inflammation etc. Therefore, the proteasome constitute an interesting target for drug discovery. Various inhibitors of this multicatalytic enzyme complex are already available. Experiments on animal models of various diseases have shown, that they can be useful anticancer, anti-inflammatory, anticachectic and antiparasital drugs. Clinical trials with at least one class of proteasome inhibitors are already conducted. The proteasome pathway is involved in the ethipathogenesis of some more groups of diseases, among them various neurodegenerative disorders. Proteasome activators and modulators can be of potential therapeutic use in these conditions.