We’ve all added nerve growth factor (NGF) to our neuronal cell cultures – perhaps with a silent plea to “Please just differentiate properly!” – but how much do you actually know about NGF? We thought we’d turn the spotlight onto neuroscience’s favorite molecule and tell you a little more about this quiet hero.
A Nobel Worthy Protein
NGF’s story began in the 1950s when scientists were studying how nerves develop in chick embryos. Rita Levi-Montalcini, an Italian developmental biologist, working alongside Viktor Hamburger, discovered how a particular tumor in mice could somehow spur the abnormal growth of nerve cells in chick embryos (1). This was an interesting finding on its own, but the more intriguing question was how the tumor actually caused nerve growth – was it directly stimulating the nerves or just messing with the normal development process?
Levi-Montalcini ran a series of experiments and managed to show that even when tumor wasn’t in direct contact with the nerves it still caused nerve growth. This led to the groundbreaking realization that whatever factor was driving this growth must be diffusing out from the tumor. Enter Stanley Cohen, an American biochemist. Cohen joined the team and was able to isolate this mysterious factor and soon showed that it was mostly made of protein along with few nucleic acids – and so, NGF was born.
The story didn’t stop there. Cohen used snake venom – known to enzymatically degrade nucleic acids – in a critical experiment. He found that instead of shutting down nerve growth, the venom actually accelerated it, revealing that snake venom contained NGF too. From there, they turned to mouse salivary glands to extract and purify NGF, a major breakthrough that eventually unlocked decades of research. By 1971, the entire amino acid sequence of NGF had been mapped (2), cementing its position in neuroscience.
In 1986, the world took notice of this significant body of research, and Levi-Montalcini and Cohen received the Nobel Prize for their discovery of NGF and epidermal growth factor (EGF), respectively. Their combined efforts showed that NGF is essential for the survival and growth of nerve cells. Today, we know NGF acts as a signaling molecule – a bit like a life coach for neurons, helping them thrive in the peripheral and central nervous systems.
The Three Faces of NGF
NGF comes in several ‘flavors,’ each with unique properties and roles. Let’s break them down:
- 7S NGF: This is a high molecular weight (~130kDa) NGF complex, made from five subunits – one β, two α, and two γ subunits – and found mostly in mouse submaxillary gland. The α and γ subunits appear to protect the biologically active β subunit from cleavage.
- proNGF: The precursor form of NGF is an intriguing character and found in human tissues as well. It’s smaller than 7S NGF (about 50 kDa) and requires further cleavage for turning into mature β-NGF. Depending on which receptor it binds to, it can either protect or damage neurons: binding sortilin/p75NTR will cause cell death, while binding TrkA/p75NTR can promote cell survival (3). It’s got a Jekyll and Hyde thing going on.
- 2.5S NGF (or β-NGF): This is the most active, pure form that neuroscientists love. composed from two identical subunits (each around 13.5 kDa) it’s responsible for nerve survival, differentiation, and growth, making it a fairly ubiquitous tool in many laboratories.
The good news? At Alomone Labs we offer all of these forms, so whether you need proNGF or 2.5S NGF, we’ve got you covered.
NGF’s Clinical Potential: From the Brain to Skin
NGF isn’t just confined to the lab. Scientists have been exploring its use in treating neurodegenerative diseases like Alzheimer’s and Parkinson’s, where it might protect neurons or help repair damaged ones. In Alzheimer’s disease, for instance, NGF might support cholinergic neurons. As these neurons deteriorate during disease progression, NGF levels drop and exacerbate the condition. Restoring NGF signaling has the potential to protect these neurons from degeneration (4).
However, it’s not all smooth sailing since it’s difficult to deliver NGF to the brain due to the blood-brain barrier. But research will continue to look at NGF-based therapies, and we even have some studies showing that enhancing NGF pathways could slow neurodegeneration and even improve cognitive function (5).
Outside the brain, NGF has a role in wound healing and corneal repair (6). Researchers have found that applying NGF topically to skin ulcers or corneal injuries (7) speeds up recovery. Who knew NGF had a future in skincare? There’s even evidence that NGF could aid recovery in traumatic brain injuries (8), adding to its ever-growing list of potential therapeutic uses.
Need NGF?
After all that, you’ve probably concluded you need to get some NGF for your lab. And if you’re already working with NGF, you know how vital it is to have a pure, stable source. That’s where Alomone Labs comes in. We’ve been making NGF for over 30 years and offer some of the purest forms on the market. Whether you need native mouse NGF 2.5S or recombinant human proNGF, we have them, and in a variety of sizes and formats – including biotinylated versions.
Not only that, but as the manufacturer and supplier, we have a stable supply and our NGF can cost significantly less than those from larger vendors, so you get the best of both worlds: high purity NGF on demand and at a reasonable price.
Recommended Reagents
Take a look at the list below and see what your lab needs.
If you need help with anything, just let us know.
References
1. W. M. Cowan, Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor. Annu Rev Neurosci 24, 551–600 (2001). DOI: https://doi.org/10.1146/annurev.neuro.24.1.551.
2. R. H. Angeletti, R. A. Bradshaw, Nerve growth factor from mouse submaxillary gland: amino acid sequence. Proc Natl Acad Sci U S A 68(10), 2417-20 (1971). DOI: http:// doi: 10.1073/pnas.68.10.2417.
3. M. S. Ioannou, M. Fahnestock, ProNGF, but Not NGF, Switches from Neurotrophic to Apoptotic Activity in Response to Reductions in TrkA Receptor Levels. Int J Mol Sci 18, 599 (2017). DOI: https://doi.org/10.3390/ijms18030599.
4. M. L. Rocco, M. Soligo, L. Manni, L. Aloe, Nerve Growth Factor: Early Studies and Recent Clinical Trials. Curr Neuropharmacol 16, 1455–1465 (2018). DOI: https://doi.org/10.2174/1570159X16666180412092859.
5. G. N. Chaldakov, L. Aloe, S. G. Yanev, M. Fiore, A. B. Tonchev, M. Vinciguerra, N. T. Evtimov, P. Ghenev, K. Dikranian, Trackins (Trk-Targeting Drugs): A Novel Therapy for Different Diseases. Pharmaceuticals (Basel) 17, 961 (2024). DOI: https://doi.org/10.3390/ph17070961.
6. L. Aloe, P. Tirassa, A. Lambiase, The topical application of nerve growth factor as a pharmacological tool for human corneal and skin ulcers. Pharmacol Res 57, 253–258 (2008). DOI: https://doi.org/10.1016/j.phrs.2008.01.010.
7. A. M. Roszkowska, L. Inferrera, E. Aragona, R. Gargano, E. I. Postorino, P. Aragona, Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin). Eur J Ophthalmol 32, 3402–3410 (2022). DOI: https://doi.org/10.1177/11206721221097584.
8. E. Atkinson, R. Dickman, Growth factors and their peptide mimetics for treatment of traumatic brain injury. Bioorg Med Chem 90, 117368 (2023). DOI: https://doi.org/10.1016/j.bmc.2023.117368.
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