Mouse proNGF Basic Research Pack

Neurotrophins are synthesized as pro-forms that can be cleaved either intracellularly to release mature, secreted ligands, or extracellularly by various proteases such as plasmin, furin, PC1/3, PC7, and PACE 4.^1,2,5 The immature precursor has a prodomain of 103 amino acids, which was thought to have a role in the folding and sorting of the mature NGF into the various secretion pathways. 

It was recently reported that proNGF, binds p75^NTR receptor preferentially over TrkA, and this selective binding of proNGF to p75^NTR  leads to apoptotic death of cells that express both TrkA and p75^NTR. However, mature NGF binds and activates both receptors, with resulting promotion of cell survival due to the TrkA-mediated survival signal overriding p75^NTR -mediated apoptotic signal.^3,4 

Since pro- and mature neurotrophins seem to elicit opposite functional effects, by differential interactions with Trks and p75^NTR receptors, extracellular cleavage represents a new way to control the synaptic functions of neurotrophins.

It was demonstrated that proNGF from injured spinal cord extracts, is active and induce apoptosis among oligodendrocytes, and apoptosis can be blocked by a proNGF-specific antibody.⁶  

Finally, proNGF was demonstrated as the predominant form in mouse, rat, and human brain tissue, thyroid, hippocampus, thus suggesting a role for proNGF in vivo.^5,7,8