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Cell signaling and neuronal death

Makoto R Hara1, Solomon H Snyder

  • 1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. mhara@jhmi.edu

Annual Review of Pharmacology and Toxicology
|August 2, 2006
PubMed

Insights

Cell death, including apoptosis, is vital in development and disease. Signaling pathways involving neurotransmitters like glutamate and intracellular calcium are key regulators, particularly in the nervous system.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Cell death is a fundamental biological process with programmed forms like apoptosis and necrosis.
  • Physiological processes, including neural development and thymus involution, utilize apoptosis.
  • Dysregulated cell death contributes to various pathologies, notably in the nervous system.

Purpose of the Study:

  • To review the roles of inter- and intracellular signaling systems in programmed cell death.
  • To highlight the specific involvement of these signaling pathways in the nervous system.
  • To discuss the contribution of neurotransmitters and intracellular messengers to excitotoxicity and neurodegeneration.

Main Methods:

  • Literature review focusing on signaling pathways in cell death.
  • Analysis of the roles of neurotransmitters (glutamate, nitric oxide) in excitotoxicity.
  • Examination of intracellular calcium signaling and its modulators (IP3 receptors, calcineurin, calpain, cytochrome c).

Main Results:

  • Glutamate and nitric oxide are identified as key neurotransmitters mediating excitotoxic cell death.
  • Intracellular calcium acts as a crucial messenger in diverse cell death pathways.
  • Proteins such as IP3 receptors, calcineurin, calpain, and cytochrome c modulate calcium-dependent cell death.

Conclusions:

  • Inter- and intracellular signaling pathways are critical regulators of programmed cell death, especially in the nervous system.
  • Excitotoxic damage, relevant to stroke and neurodegenerative diseases, involves specific neurotransmitter signaling.
  • Intracellular calcium dynamics, modulated by various proteins, play a central role in mediating cell death outcomes.

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