Apoptosis, excitotoxicity, and neuropathology

Exp Cell Res. 1998 Mar 15;239(2):183-201. doi: 10.1006/excr.1997.4026.


While a high rate of cell loss is tolerated and even required to model the developing nervous system, an increased rate of cell death in the adult nervous system underlies neurodegenerative disease. Evolutionarily conserved mechanisms involving proteases, Bcl-2-related proteins, p53, and mitochondrial factors participate in the modulation and execution of cell death. In addition, specific death mechanisms, based on specific neuronal characteristics such as excitability and the presence of specific channels or enzymes, have been unraveled in the brain. Particularly important for various human diseases are excessive nitric oxide (NO) production and excitotoxicity. These two pathological mechanisms are closely linked, since excitotoxic stimulation of neurons may trigger enhanced NO production and exposure of neurons to NO may trigger the release of excitotoxins. Depending on the experimental situation and cell type, excitotoxic neuronal death may either be apoptotic or necrotic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Apoptosis* / drug effects
  • Brain / metabolism
  • Brain / pathology*
  • Brain Diseases / metabolism
  • Brain Diseases / pathology*
  • Endopeptidases / metabolism
  • Genes, bcl-2
  • Genes, p53
  • Growth Substances / physiology
  • Humans
  • Mitochondria / physiology
  • Models, Neurological
  • Necrosis
  • Nerve Degeneration
  • Nerve Tissue Proteins / physiology
  • Neuroglia / pathology
  • Neurons / drug effects
  • Neurons / pathology
  • Neurotoxins / pharmacology*
  • Nitric Oxide / metabolism
  • PC12 Cells
  • Poly(ADP-ribose) Polymerases / physiology
  • Rats


  • Growth Substances
  • Nerve Tissue Proteins
  • Neurotoxins
  • Nitric Oxide
  • Poly(ADP-ribose) Polymerases
  • Endopeptidases