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Cross-linking of NCAM receptors on neurons induces programmed cell death

B Y Azizeh1, D H Cribbs, V M Kreng

  • 1Department of Psychobiology, Institute for Brain Aging and Dementia, University of California, Irvine 92697-4540, USA. abassem@maryanne.bio.uci.edu

Brain Research
|August 5, 1998
PubMed

Insights

Soluble anti-neural cell adhesion molecule (NCAM) antibodies trigger programmed cell death in neurons, revealing specific receptor pathways involved in neurodegeneration.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Programmed cell death contributes to neuronal loss in neurodegenerative diseases.
  • Stimuli initiating programmed cell death in neurons are of significant research interest.
  • Previous work demonstrated concanavalin A-induced neuronal cell death via receptor cross-linking.

Purpose of the Study:

  • To investigate whether specific cell surface receptors can initiate programmed cell death in neurons.
  • To determine if neural cell adhesion molecules (NCAM) are involved in initiating neuronal apoptosis.

Main Methods:

  • Cortical neurons were cultured and treated with soluble anti-NCAM monoclonal antibodies.
  • Neuronal cell death was assessed after 24 hours.
  • Morphological and biochemical features of apoptosis were examined, including DNA fragmentation.

Main Results:

  • Soluble anti-NCAM monoclonal antibodies induced significant neuronal cell death within 24 hours.
  • Treated neurons exhibited characteristic apoptotic features: membrane blebbing, cell shrinkage, nuclear chromatin condensation, and internucleosomal DNA cleavage.
  • Immobilized anti-NCAM antibodies supported neuronal adhesion and outgrowth, contrasting with soluble antibody effects.

Conclusions:

  • Specific neural cell adhesion molecules (NCAM) can act as triggers for programmed cell death in neurons.
  • Soluble anti-NCAM antibodies induce apoptosis, suggesting a role for NCAM signaling in neurodegenerative processes.
  • Understanding these specific receptor-mediated death pathways is crucial for developing therapeutic strategies for neurodegenerative diseases.

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