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Role of µ-Calpain I and Lysosomal Cathepsins in Hippocampal Neuronal Necrosis After Transient Global Ischemia in Primates

  • Anton B. Tonchev
  • Tetsumori Yamashima
Chapter

Abstract

Transient global cerebral ischemia inflicts damage on selective neuronal populations. The most sensitive of these are pyramidal neurons in the cornu Ammonis (CA) 1 sector of the hippocampus. In contrast to focal ischemic insult, neuronal death after global ischemia is postponed by a few days, then designated delayed neuronal death (DND). This time lag provides scientists with the intriguing opportunity of using this time window to counteract the pro-death mechanisms. The latter have been a subject of intensive investigations for more than two decades, with different types of cell demise put on the scene, including necrosis, apoptosis, and autophagy. Here, we shall review the molecular events known to occur in a primate model of transient global cerebral ischemia,0 focusing on the enzymes µ-calpain and cathepsin(s), and their involvement in neuronal necrosis. A decade after the “calpain–cathepsin hypothesis” of DND had been proposed, a paradigm shift is occurring in our understanding of necrosis. It was classically considered to be an uncontrolled and poorly regulated process, while recent evidence seems to suggest that necrosis is a highly orchestrated and evolutionally conserved program of cell death. Calpain and cathepsins appear to be central molecular players in this program, and thus represent appropriate molecular targets for neuroprotection.

Keywords

Necrotic Cell Death Autophagosome Formation Calpain Inhibitor Neuronal Necrosis Global Brain Ischemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Restorative NeurosurgeryKanazawa University Graduate School of Medical ScienceKanazawaJapan

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