Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Acknowledgments
- Part I Special lectures
- 1 Zinc toxicity in the ischemic brain
- 2 Central nervous system ischemia: diversity among the caspases
- Part II Oxidative stress
- Part III Apoptosis
- Part IV Hot topics
- Part V Hemorrhage, edema and secondary injury
- Part VI Inflammation
- Part VII Gene transfer and therapy
- Part VIII Neurogenesis and plasticity
- Part IX Magnetic resonance imaging in clinical stroke
- Part X Risk factors, clinical trials and new therapeutic horizons
- Index
- Plate section
2 - Central nervous system ischemia: diversity among the caspases
from Part I - Special lectures
Published online by Cambridge University Press: 02 November 2009
- Frontmatter
- Contents
- List of contributors
- Preface
- Acknowledgments
- Part I Special lectures
- 1 Zinc toxicity in the ischemic brain
- 2 Central nervous system ischemia: diversity among the caspases
- Part II Oxidative stress
- Part III Apoptosis
- Part IV Hot topics
- Part V Hemorrhage, edema and secondary injury
- Part VI Inflammation
- Part VII Gene transfer and therapy
- Part VIII Neurogenesis and plasticity
- Part IX Magnetic resonance imaging in clinical stroke
- Part X Risk factors, clinical trials and new therapeutic horizons
- Index
- Plate section
Summary
Introduction
Ischemic neurons die acutely by osmotically driven rupture of cellular and subcellular membranes by a process called necrosis, but may also die in a delayed manner, dependent on the activation of a family of cysteine proteases named caspases. Caspases are synthesized as inactive proenzymes containing three subunits, an N-terminal prodomain, a large (∼20 kDa) and a small subunit (∼10 kDa), which form heterotetromers on cleavage and activation. Family members show a near absolute specificity for cleavage at the N-terminal of aspartate residues. At least 14 caspases have been identified to date, designated 1 to 14. Caspases −1, −2, −3, −7, −8 and −9 are constitutively expressed in the brain. In the spinal cord, caspases −2, −3 and −8 are constitutively expressed. Caspases −1, −4 and −5 (caspase-1 family members) promote cytokine maturation and mediate inflammation whereas caspases −2, −3, −6, −7, −8 and −9 (caspase-3 family members) promote apoptotic cell death. On activation, caspase-11, which is found only in mice, promotes both cytokine maturation and apoptosis.
In this review, we will briefly summarize the evidence implicating caspases in cerebral and spinal cord ischemia. Caspase-driven cell death may have important therapeutic implications for ischemia as well as for other acute and chronic central nervous system (CNS) conditions in which cell death is prominent.
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- Chapter
- Information
- Cerebrovascular Disease22nd Princeton Conference, pp. 9 - 20Publisher: Cambridge University PressPrint publication year: 2002