| 1. |
- Cassens, U., et al.
(author)
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Viral modulation of cell death by inhibition of caspases
- 2003
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In: Archivum Immunologiae et Therapiae Experimentalis. - 0004-069X .- 1661-4917. ; 51:1, s. 19-27
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Research review (peer-reviewed)abstract
- Caspases are key effectors of the apoptotic process. Some of them play important roles in the immune system, being involved in the proteolytic maturation of the key cytokines, including interleukin 1beta (IL-1beta) and IL-18. The latter directs the production of interferon gamma (IFN-gamma). Among pathogens, particularly viruses express various modulators of caspases that inhibit their activity by direct binding. By evading the apoptotic process, viruses can better control their production in the infected cell and avoid the attack of the immune system. Targeting the maturation of the key cytokines involved in the initiation of (antiviral) immune response helps to avoid recognition and eradication by the immune system. The three main classes of caspase inhibitors frequently found among viruses include serine proteinase inhibitors (serpins: CrmA/SPI-2), viral IAPs (vIAPs) and p35. Their molecular mechanisms of action, structures and overall influence on cellular physiology are discussed in the review below.
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| 2. |
- Kreuter, M., et al.
(author)
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Stroke, myocardial infarction, acute and chronic inflammatory diseases : caspases and other apoptotic molecules as targets for drug development
- 2004
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In: Archivum Immunologiae et Therapiae Experimentalis. - 0004-069X .- 1661-4917. ; 52:3, s. 141-155
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Research review (peer-reviewed)abstract
- Mapping of the human and other eukaryotic genomes has provided the pharmacological industry with excellent models For drug discovery. Control of cell proliferation, differentiation, activation and cell removal is crucial for the development and existence of multicellular organisms. Each cell cycle progression, with sequences of DNA replication, mitosis, and cell division, is a tightly controlled and complicated process that, 1 when deregulated, may become dangerous not only to a single cell, but also to the whole organism. Regulation and the proper control of the cell cycle and of programmed cell death (apoptosis) is therefore essential for mammalian development and the homeostasis of the immune system. The molecular networks that regulate these processes are critical targets for drug development, gene therapy, and metabolic engineering. In addition to the primary, intracellular apoptotic suicide machinery, components of the immune system can detect and remove cells and tissue fragments that no longer serve their defined functions. In this review we will focus on apoptotic pathways converging on caspase family proteases, summarizing pharmacological attempts that target genes, proteins, and intermolecular interactions capable of modulating apoptosis and the inflammatory response. The upcoming pharmacological development for treatment of acute pathologies, such as sepsis, SIRS, stroke, traumatic brain injury, myocardial infarction, spinal cord injury, acute liver failure, as well as chronic disorders Such as Huntington's disease, Parkinson's disease, ALS, and rheumatoid arthritis, will be discussed in details. We also suggest new potential molecular targets that may prove to be effective in controlling apoptosis and the immune response in vivo.
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| 3. |
- Sadowski-Debbing, K., et al.
(author)
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Caspases - Their role in apoptosis and other physiological processes as revealed by knock-out studies
- 2002
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In: Archivum Immunologiae et Therapiae Experimentalis. - 0004-069X .- 1661-4917. ; 50:1, s. 19-34
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Research review (peer-reviewed)abstract
- Caspases are crucial mediators of apoptosis, a form of physiological cell death. Their activation is carefully controlled by a philogenetically conserved death program, which is indispensable for the homeostasis and development of higher organisms. Dysregulation of apoptosis contributes to the pathogenesis of many human diseases. As effectors of the apoptotic machinery, caspases are considered potential therapeutic targets. In vitro studies have demonstrated the requirement of caspase activity for both the triggering phase as well as the execution of apoptosis, thus providing a molecular base for the time-tuning of this process by pharmacological agents. The precise roles of the individual caspases in vivo and their functional relation to each other have been best demonstrated in genetically modified animals. The generation of single caspase-deficient mice have confirmed most of the data obtained in vitro and exposed some new aspects previously undetected in the cell culture system. Interestingly, inactivation of many caspases revealed not only their expected participation in apoptotic events as well as in the maturation of cytokines, but also provided hints about the role of at least some caspases in cell differentiation and stimulatory responses. In this review we will discuss what these studies have unveiled about the role of individual caspases in development, apoptosis, and inflammation, with particular focus on their role beyond the apoptotic process.
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| 6. |
- Martin-Fontecha, A, et al.
(author)
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The social life of NK cells
- 2001
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In: Archivum immunologiae et therapiae experimentalis. - 0004-069X. ; 4949 Suppl 1, s. S33-S39
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Journal article (peer-reviewed)
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| 7. |
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