ProNGF: a neurotrophic or an apoptotic molecule?
Nerve growth factor (NGF) acts on various classes of central and peripheral neurons to promote cell survival, stimulate neurite outgrowth and modulate differentiation. NGF is synthesized as a precursor, proNGF, which undergoes processing to generate mature NGF. It has been assumed, based on studies in the mouse submandibular gland, that NGF in vivo is largely mature NGF, and that mature NGF accounts for the molecule's biological activity. However, recently we have shown that proNGF is abundant in central nervous system tissues whereas mature NGF is undetectable, suggesting that proNGF may have a function distinct from its role as a precursor. A recent report that proNGF has apoptotic activity contrasts with other data demonstrating that proNGF has neurotrophic activity. This chapter will review the structure and processing of NGF and what is known about the biological activity of proNGF. Possible reasons for the discrepancies in recent reports are discussed.
Fahnestock
Margaret
M
Department of Psychiatry and Behavioral Neurosciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada. fahnest@mcmaster.ca
Yu
Guanhua
G
Coughlin
Michael D
MD
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007239:Infections; D007313:Insecta; D007525:Isoelectric Focusing / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020932:Nerve Growth Factor / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D002352:Carrier Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; C061397:pro-nerve growth factor, human; C489226:pro-nerve growth factor, mouse; D020932:Nerve Growth Factor; D020917:Receptor, trkA