Neurotrophic factors


Neurotrophic factors are a family of proteins that are responsible for the growth and survival of developing neurons and the maintenance of mature neurons.

The neurotrophic factors consists of a class of growth factors that are capable of signaling particular cells to survive, differentiate, or grow.

There are three known families of neurotrophic factors:

1. Neurotrophins, which include four neurotrophic factors:

  • nerve growth factor (NGF),
  • brain-derived neurotrophic factor (BDNF),
  • neurotrophin-3 (NT-3), and
  • neurotrophin-4 (NT-4) which promote the survival of existing neurons while stimulating the growth of new neurons.

2. GDNF family of ligands (GFL) which include four neurotrophic factors:

  • glial cell line-derived neurotrophic factor (GDNF),
  • neurturin (NRTN),
  • artemin (ARTN), and
  • persephin (PSPN) which pertain to cell survival, neurite outgrowth, cell differentiation and cell migration.

3. Ciliary Neurotrophic Factor

Ciliary Neurotrphic Factor promotes neurite outgrowth in certain neural populations including astrocytes.

The following substances may enhance the function of the various neurotrophic factors:

Acetyl L-Carnitine (ALCAR)

Wollen KA. Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Altern Med Rev. 2010 Sep;15(3):223-44

Taglialatela, G., et al. Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Experimental Gerontology. 29(1):55-66, 1994.

Codonopsis (Chinese Tang Shen Root)

Liu, J. H., et al. Codonopsis pilosula (Franch) Nannf total alkaloids potentiate neurite outgrowth induced by nerve growth factor in PC12 cells. Acta Pharmacol Sin. 24(9):913-917, 2003.


Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons

Docosahexaenoic Acid (DHA)

Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004 Oct;21(10):1457-67.

Cole, G. M., et al. DHA may prevent age-related dementia. Journal of Nutrition. 2010.

Jiang, L. H., et al. The influence of orally administered docosahexaenoic acid on cognitive ability in aged mice. J Nutr Biochem. 2008.

Huperzine A

Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells


Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer’s disease


Shinoda, I., et al. Lactoferrin promotes nerve growth factor synthesis/secretion in mouse fibroblast L-M cells. Advances in Experimental Medicine and Biology. 357:279-385, 1994.

Lion’s Mane Mushroom (Hericium erinaceus)

Effect of an exo-polysaccharide from the culture broth of Hericium erinaceus on enhancement of growth and differentiation of rat adrenal nerve cells


GSK-3 as a Target for Lithium-Induced Neuroprotection Against Excitotoxicity in Neuronal Cultures and Animal Models of Ischemic Stroke


Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients


Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala


Tang, Y. P., et al. Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (-)-deprenyl and melatonin treatments. J Neurosci Res. 53(5):593-604, 1998.

Chen, K. B., et al. Oxidative injury to the locus coeruleus of rat brain: neuroprotection by melatonin. J Pineal Res. 35(2):109-117, 2003.

Armstrong, K. J., et al. Induction of GDNF mRNA expression by melatonin in rat C6 glioma cells. Neuroreport. 13(4):473-475, 2002.

Polygala tenuifolia (Chinese Senega Root)

Yabe, T., et al. Induction of NGF synthesis in astrocytes by onjisaponins of Polygala tenuifolia, constituents of kampo (Japanese herbal) medicine, Ninjin-yoei-to. Phytomedicine. 10(2-3):106-114, 2003.

Proline-rich polypeptides (colostrinin)

Leszek et al. Colostrinin proline-rich polypeptide complex from ovine colostrum–a long-term study of its efficacy in Alzheimer’s disease. Med Sci Monit. 2002 Oct;8(10):PI93-6.

Janusz M, Zablocka A. Colostral proline-rich polypeptides–immunoregulatory properties and prospects of therapeutic use in Alzheimer’s disease.

Pyrroloquinoline Quinone (PQQ)

Enhanced rat sciatic nerve regeneration through silicon tubes filled with pyrroloquinoline quinone

Nakano M, Ubukata K, Yamamoto T, Yamaguchi H. Effect of Pyrroloquinoline Quinone (PQQ) on Mental Status of Middle-Aged and Elderly Persons. 2007

Zhang L, Liu J, Cheng C, Yuan Y, Yu B, Shen A, Yan M. The neuroprotective effect of pyrroloquinoline quinone on traumatic brain injury. J Neurotrauma. 2012 Mar 20;29(5):851-64. Epub 2011 Dec 20.

Rehmannia (Rehmannia glutinosa, aka Chinese Foxglove)

Yu, H., et al. Rehmannia glutinosa induces glial cell line-derived neurotrophic factor gene expression in astroglial cells via cPKC and ERK1/2 pathways independently. Pharmacol Res. 2006.

Rosemary (Carnosic Acid)

Kosaka, K., et al. Carnosic acid, a component of rosemary (Rosmarinus officinalis L.), promotes synthesis of nerve growth factor in T98G human glioblastoma cells. Biol Pharm Bull. 26(11):1620-1622, 2003.


Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes


Wang, L., et al. Dietary uridine-5′-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 27(1):137-145, 2005.

Vitamin A

Kheirvari, S., et al. High-dose dietary supplementation of vitamin A induces brain-derived neurotrophic factor and nerve growth factor production in mice with simultaneous deficiency of vitamin A and zinc. Nutr Neurosci. 11(5):228-234, 2008.

Vitamin D3

McGrath, J. J., et al. Vitamin D(3)-implications for brain development. J Steroid Biochem Mol Biol. 89-90:557-560, 2004.

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