## Abstract Following the discovery of the human kinome, protein kinases have become the second most important group of drug targets as they can be modulated by small ligand molecules. Moreover, orally active protein kinase inhibitors have recently reached the market and there are many more in clin
Caspases as treatment targets in stroke and neurodegenerative diseases
✍ Scribed by Jörg B. Schulz; Michael Weller; Michael A. Moskowitz
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 975 KB
- Volume
- 45
- Category
- Article
- ISSN
- 0364-5134
No coin nor oath required. For personal study only.
✦ Synopsis
Apoptosis is one of the most exciting and intensely investigated areas of biology and medicine today. Cysteine proteases called caspases serve as the executioners of apoptosis, a form of cell suicide. Hypoxic/ischemic cell death proceeds in part, by apoptosis, particularly within the periinfarct zone or ischemic penumbra. During ischemia, activated caspases dismantle the cell by cleaving multiple substrates including cytoskeletal proteins and enzymes essential for cell repair. Strategies that inhibit caspase activity block cell death in experimental models of mild ischemia, and preserve neurological function. The therapeutic window for caspase inhibition is substantially longer than for glutamate receptor antagonists, and treatment combinations with both classes of drugs decrease ischemic injury and expand the treatment window synergistically. Hence, the caspases are now recognized as novel therapeutic targets for central nervous system diseases in which cell death is prominent. This article will review the evidence and the potential importance of caspase inhibition to cerebral ischemia and briefly summarize an emerging body of data implicating caspases in cell death accompanying neurodegenerative disorders.
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In order to develop novel central acting drugs, the modulation of intracellular Ca 2 dynamics must be considered as an essential factor, since following excessive Ca 2 in¯ux to neuronal cells, abnormal intracellular Ca 2 concentrations induce several types of mental and neurological disorders. This