ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury

Neuron. 2002 Oct 24;36(3):375-86. doi: 10.1016/s0896-6273(02)01005-x.


The neurotrophin receptor p75 is induced by various injuries to the nervous system, but its role after injury has remained unclear. Here, we report that p75 is required for the death of oligodendrocytes following spinal cord injury, and its action is mediated mainly by proNGF. Oligodendrocytes undergoing apoptosis expressed p75, and the absence of p75 resulted in a decrease in the number of apoptotic oligodendrocytes and increased survival of oligodendrocytes. ProNGF is likely responsible for activating p75 in vivo, since the proNGF from the injured spinal cord induced apoptosis among p75(+/+), but not among p75(-/-), oligodendrocytes in culture, and its action was blocked by proNGF-specific antibody. Together, these data suggest that the role of proNGF is to eliminate damaged cells by activating the apoptotic machinery of p75 after injury.

Publication types

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

MeSH terms

  • Animals
  • Antibody Specificity / immunology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Autophagy-Related Proteins
  • Caspase 3
  • Caspases / metabolism
  • Cell Survival / physiology
  • Female
  • Gene Expression Regulation / physiology
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Growth Factor / immunology
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • Oligodendroglia / metabolism*
  • Protein Precursors / immunology
  • Protein Precursors / metabolism*
  • Protein Precursors / pharmacology
  • Proteins / metabolism
  • Reaction Time / physiology
  • Receptor, Nerve Growth Factor / deficiency*
  • Receptor, Nerve Growth Factor / drug effects
  • Receptor, Nerve Growth Factor / genetics
  • Recombinant Fusion Proteins
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / physiopathology


  • Autophagy-Related Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein Precursors
  • Proteins
  • Rb1cc1 protein, mouse
  • Receptor, Nerve Growth Factor
  • Recombinant Fusion Proteins
  • pro-nerve growth factor, mouse
  • Nerve Growth Factor
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases