Caspases as treatment targets in stroke and neurodegenerative diseases

Caspases as treatment targets in stroke and neurodegenerative diseases 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. Ann Neurol 1999;45:421–429 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Caspases as treatment targets in stroke and neurodegenerative diseases

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Publisher
Wiley
Copyright
Copyright © 1999 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
D.O.I.
10.1002/1531-8249(199904)45:4<421::AID-ANA2>3.0.CO;2-Q
Publisher site
See Article on Publisher Site

Abstract

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. Ann Neurol 1999;45:421–429

Journal

Annals of NeurologyWiley

Published: Apr 1, 1999

References

  • Endonucleolytic DNA fragmentation is not required for apoptosis of cultured rat cerebellar granule neurons
    Schulz, Schulz; Beinroth, Beinroth; Weller, Weller
  • Ultrastructural morphological changes are not characteristic of apoptotic cell death following focal cerebral ischaemia in the rat
    Campagne, Campagne; Gill, Gill
  • Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis
    Sakahira, Sakahira; Enari, Enari; Nagata, Nagata
  • Caspase inhibition selectively reduces the apoptotic component of oxygen‐glucose deprivation‐induced cortical neuronal cell death
    Gottron, Gottron; Ying, Ying; Choi, Choi
  • Differential regulation of Bax, Bcl‐2, and Bcl‐x proteins in focal cortical ischemia in the rat
    Isenmann, Isenmann; Stoll, Stoll; Schroeter, Schroeter
  • DNA fragmentation in granular cells of human cerebellum following global ischemia
    Hara, Hara; Yoshimi, Yoshimi; Hirose, Hirose
  • Ischemia‐induced neuronal apoptosis
    Choi, Choi
  • Additive neuroprotective effects of dextrorphan and cycloheximide in rats subjected to transient focal cerebral ischemia
    Du, Du; Hu, Hu; Csernansky, Csernansky

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