| Nerve Growth Factor (NGF) | ||
|---|---|---|
| Protein Name | Beta-nerve growth factor | |
| Gene | NGF | |
| UniProt ID | Protein Family | Neurotrophin |
| Structure | Homodimer, each subunit ~120 aa | |
| Molecular Weight | ~26 kDa (dimer) | |
| Receptors | TrkA (NTRK1), p75NTR (TNFRSF1B) | |
| Subcellular Localization | Secreted, extracellular | |
| Expression | Brain, peripheral nervous system, immune cells | |
| Disease Associations | Alzheimer's Disease, Peripheral Neuropathy | |
Nerve Growth Factor (Ngf) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Nerve Growth Factor (NGF) is the prototypical member of the neurotrophin family of growth factors, playing a fundamental role in the development, maintenance, and plasticity of specific neuronal populations in both the central and peripheral nervous systems. As the first growth factor ever discovered, NGF has served as a paradigm for understanding neurotrophic factor biology and remains a major focus of research in neurodegenerative diseases and neural repair.1
NGF is synthesized as a pre-propeptide that undergoes proteolytic processing:
The three-dimensional structure reveals a homodimer with each monomer containing a cysteine knot motif, a characteristic of the neurotrophin family.2
During development, NGF is essential for:
In the adult nervous system, NGF continues to modulate:
The high-affinity TrkA receptor mediates the classic neurotrophic effects of NGF:[3]
The p75 neurotrophin receptor modulates NGF responses:[4]
NGF therapy has been investigated for AD due to:[3]
Clinical approaches have included:
Clinical trials have explored NGF for:
The discovery of NGF by Rita Levi-Montalcini and Stanley Cohen in the 1950s revolutionized neuroscience:1
The study of Nerve Growth Factor (Ngf) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Levi-Montalcini R. The nerve growth factor: thirty-five years later. Science. 1987;237(4819):1154-1162. DOI:10.1126/science.2880399
Wiesmann C, Ultsch MH, Bass SH, de Vos AM. Crystal structure of nerve growth factor at 2.6 Å resolution. Structure. 1996;4(2):147-154. DOI:10.1016/S0969-2126(9600018-0
Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003;4(4):299-309. DOI:10.1038/nrn1078
Hempstead BL. The many faces of p75NTR. Curr Opin Neurobiol. 2002;12(3):260-267. DOI:10.1016/S0959-4388(0200321-5
Longo FM, Massucci S, Zaccaria ML, et al. Small molecule NGF mimetics: a novel therapeutic approach for Alzheimer's disease. J Mol Neurosci. 2007;33(2):141-147. DOI:10.1007/s12031-007-0081-3
Tuszynski MH, Thal L, UHS M, et al. Nerve growth factor gene therapy for Alzheimer's disease. Nat Med. 2005;11(5):551-555. DOI:10.1038/nm1239
Cattaneo A, Calissano P. Nerve growth factor and Alzheimer's disease: new facts for an old hypothesis. Mol Neurobiol. 2012;46(3):588-604. DOI:10.1007/s12035-012-8288-3
Allen SJ, Watson JJ, Shoemark KD, Williams NH, Patel DK. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther. 2013;138(2):155-175. DOI:10.1016/j.pharmthera.2013.01.004
Sebollela A, CTemporaryTarget V, Sathler LB, et al. Amyloid-beta oligomers induce differential gene expression in human neural cells. Mol Neurobiol. 2019;56(7):5083-5094. DOI:10.1007/s12035-018-1421-1
Mufson EJ, Counts SE, Perez SE, Binder LI. Cholinergic system during the progression of Alzheimer's disease: therapeutic implications. J Alzheimers Dis. 2008;15(4):545-567. DOI:10.3233/JAD-2008-15102
Schliebs R, Arendt T. The cholinergic system in aging and neuronal degeneration. Behav Brain Res. 2011;221(2):555-563. DOI:10.1016/j.bbr.2010.11.058
Eriksdotter Jönhagen M, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 1998;9(5):246-257. DOI:10.1159/000017059
Williams BJ, Eriksdotter-Jönhagen M, Granholm AC. Nerve growth factor in treatment and pathogenesis of Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(5):833-840. DOI:10.1016/j.pnpbp.2006.01.023
About-Samar R, Sidhu PS, Dixon K. Nerve growth factor and Alzheimer's disease: new facts for an old hypothesis. Neural Regen Res. 2020;15(12):2195-2204. DOI:10.4103/1673-5374.284009
Ibáñez CF, Simi A. p75 neurotrophin receptor signaling in nervous system injury and degeneration: paradoxes and potentials. Exp Neurol. 2012;235(1):53-61. DOI:10.1016/j.expneurol.2011.12.032