NGF/NGF-β ELSIA Kit, Human

BACKGROUND Nerve Growth Factor (NGF) is a small secreted protein and a member of neurotrophin family, which also includes Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin 4/5 (NT-4/5). All the neurotrophins are initially produced as 30–35 kDa precursor proteins containing a signal peptide, sites for glycosylation, and pairs of basic amino acids that are recognized by processing enzymes. The calcium-dependent serine protease furin and other members of the prohormone convertase family cleave each of the neurotrophins at a dibasic cleavage site in the middle of the precursor protein, releasing the biologically active 12–14 kDa C-terminal product. NGF plays important roles in the growth, maintenance, and survival of certain target sympathetic and sensory neurons. Without it, these neurons undergo apoptosis. NGF causes axonal growth. Studies have shown that it causes axonal branching and a bit of elongation. NGF plays a role in the repair, regeneration, and protection of neurons. Thus, it could serve as a therapeutic agent in neurodegenerative conditions such as Alzheimer's disease. NGF has also been suggested to play a role in other physiological systems and tissues such as the immune system. There is evidence that NGF circulates throughout the entire body and is important for maintaining homeostasis. There is also evidence that shows that the precursor to NGF, pro-NGF, may also play important roles due to its abundance. These include apoptotic and neurotrophic properties.¹

NGF binds with at least two classes of receptors: p75NTR (low affinity nerve growth factor receptor, which belong to the death receptor family) and TrkA, a transmembrane tyrosine kinase. NGF may signal its neuroprotective actions through the tyrosine kinase TrkA receptor and trigger apoptosis in some cells through the p75 receptor in absence of TrkA. High-affinity binding of NGF requires both TrkA and p75NTR. Both are associated with neurodegenerative disorders. NGF binds to high-affinity tyrosine kinase receptor, TrkA, resulting in activation and autophosphorylation of TrkA, which is coupled to the Ras, Cdc42/Rac/RhoG, MAPK, PI 3-K and PLCgamma signaling pathways.² The downstream effectors of the ras pathway include activation of fos and jun to form AP-1, activating genes through this transcription factor. Other transcription factors involved in NGF responses include Egr and CREB. The Egr family of transcription factors as well as the Mek/Erk pathway contribute to NGF-induced neurite formation. The CREB family of transcription factors are involved in NGF-induced survival of sympathetic neurons.

There are four members of the Trk family; TrkA, TrkB and TrkC and a related p75NTR receptor. p75NTR lacks tyrosine kinase activity and signals via NF-kappaB activation. Each family member binds different neurotrophins with varying affinities. TrkA potently binds nerve growth factor (NGF) and is involved in differentiation and survival of neurons and in control of gene expression of enzymes involved in neurotransmitter synthesis. TrkB has highest affinity for brain-derived neurotrophic factor (BDNF) and is involved in neuronal plasticity, longterm potentiation and apoptosis of CNS neurons. TrkC is activated by neurotrophin-3 (NT-3) and is found on proprioceptive sensory neurons. p75NTR binds neurotrophin precursors with high affinity and retains low affinity to the mature cleaved forms. TrkA was originally identified as an oncogene as it is commonly mutated in cancers, particularly colon and thyroid carcinomas.³

 

REFERENCES  

1. Sofroniew, M.V. et al: Ann. Rev. Neurosci. 24:1217-81, 2001
2. Delcroix, J-D. et al: Neuron 39:69-84, 2003
3. Barbacid, M.: J. Neurobiol. 25:1386-403, 1994 
 

 

ELISA Kits are based on standard sandwich enzyme-linked immunosorbent assay technology. Freshly prepared standards, samples, and solutions are recommended for best results.