Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury Academic Article uri icon

Overview

MeSH Major

  • Cell Death
  • Central Nervous System
  • Nerve Growth Factor
  • Protein Precursors

abstract

  • The unprocessed precursor of the neurotrophin nerve growth factor (NGF), proNGF, has been suggested to be a death-inducing ligand for the neurotrophin receptor p75. Whether proNGF is a true pathophysiological ligand that is secreted, binds p75, and activates cell death in vivo, however, has remained unknown. Here, we report that after brain injury, proNGF was induced and secreted in an active form capable of triggering apoptosis in culture. We further demonstrate that proNGF binds p75 in vivo and that disruption of this binding results in complete rescue of injured adult corticospinal neurons. These data together suggest that proNGF binding to p75 is responsible for the death of adult corticospinal neurons after lesion, and they help to establish proNGF as the pathophysiological ligand that activates the cell-death program by means of p75 after brain injury. Interference in the binding of proNGF to p75 may provide a therapeutic approach for the treatment of disorders involving neuronal loss.

publication date

  • April 20, 2004

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC395951

Digital Object Identifier (DOI)

  • 10.1073/pnas.0305755101

PubMed ID

  • 15026568

Additional Document Info

start page

  • 6226

end page

  • 30

volume

  • 101

number

  • 16