BUY proNGF (Mut-human)

proNGF (Mut-human)
proNerve Growth Factor (Mutated-human)
Recombinant, E. coli

The proneurotrophins (proNT) are, as their name suggests, the proform of the neurotrophins. The neurotrophins (NT) are a family of soluble, basic growth factors which regulate neuronal development, maintenance, survival and death in the CNS and the PNS. They exert their biological effects by binding to two types of receptors: the Trk receptors, and the p75^NTR receptor. Like many other proteins, mature NT arise from the proteolytic cleavage of the precursor form by various proteases: plasmin, furin, MP7, PC1/3, PC2, PC5/6, PC7 and PACE4, which cut behind a pair or even a single basic residue. This has been known for many years, and it was thought that the roles of the prodomain were to aid in the folding of the mature protein and to sort the mature neurotrophin into the various secretion pathways. However, recently an assortment of papers have been published which suggest new roles for the proNT.

It has been found that proNerve Growth Factor (proNGF), and not mature NGF, is the predominant isoform found in the human brain as well as in a variety of cell types, including mast cells, sciatic nerve cells, thyroid gland, skeletal muscle, prostate gland, hippocampus and hair follicle. Thus, the case of the mouse salivary gland, which is the most abundant source of mature NGF, seems to be the exception and not the rule.

proNGF is the ligand preferred by p75^NTR. Therefore, cleavage resistant proNGF (mutated at the cleavage site to insure that it retains the prodomain) induced apoptosis ten times more effectively than� mature NGF in a vascular smooth muscle cell line expressing p75^NTR but not Trk receptors. However, proNGF can also mediate survival. Rattenholl et al. have shown that proNGF was as effective as NGF in inducing survival of DRG neurons. Fahnestock et al>/i> have shown that a mutated proNGF exhibits neurite outgrowth on both PC12 cells and mouse sympathetic cervical ganglions.

A neccesary but not sufficient partner for proNGF is sortilin, a 95 kDa member of the Vps10p domain receptor family which is expressed in a variety of tissues, notably brain, spinal tissue and muscle. However, not all cells expressing p75^NTR and sortilin react to proNGF by becoming apoptotic. For example, in mature pig oligodendrocytes, which express p75^NTR and sortilin, proNGF induces survival.

Alomone Labs is pleased to make available a series of novel proNGF preparations to aid in the clarification of this interesting scientific issue.

Neurotrophic Factors, Nerve Growth Factors, NGF