Natural and synthetic inhibitors of caspases: targets for novel drugs

Current Drug Targets. CNS and Neurological Disorders
Brigitte Onténiente

Abstract

Along with inflammation, apoptosis appears a common feature of cell death in non-infectious neurodegenerative diseases. The apoptotic program is an energy-requiring, slowly developing process that evolves in three main steps; initiation, progression and execution. Each step of the program is controlled by a number of molecules with synergistic or antagonistic functions, among which the family of cystein proteases called caspases has a primary role. The central position of caspases in all steps of the apoptotic process had led to the development of several families of inhibitory drugs based on the tetrapeptidic sequence of their preferred cleavage site on target molecules. The initial classes of compounds had problems of toxicity, specificity and blood brain barrier penetration, but even so, gave encouraging preclinical results in animal models of neurological diseases. New generations of anti-caspase drugs have been developed, including non peptide-based compounds, which have shown satisfactory pharmaceutical activity. In addition, pre-clinical developments include advances in protein therapy based on the use of natural inhibitors of caspases, which possess the advantage of targeting synergistic neuroprotective pathways. This s...Continue Reading

Citations

Sep 10, 2008·Apoptosis : an International Journal on Programmed Cell Death·Guoxing FuIrene T Weber
Oct 24, 2009·Médecine sciences : M/S·Régis BordetCatherine Heurteaux
Aug 24, 2005·Antioxidants & Redox Signaling·Ronald JemmersonNickolay Brustovetsky
Jul 8, 2009·International Journal of Molecular Sciences·Yahya E ChoonaraSibongile R Sibambo
Jun 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yves SabbaghMarie B Demay
Dec 20, 2005·Neurobiology of Disease·Christelle GuéganBrigitte Onténiente
Dec 6, 2005·Brain Research Bulletin·Gunnar P H Dietz, Mathias Bähr

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