FG Loop Peptide (FGL)

Potential Benefits of FG Loop Peptide

• Treats stroke and traumatic brain injuries [1-12]
• Improves cognitive function [13-25]
• Wards off depression [26-30]
• Fights inflammation [31-35]

What is FG Loop Peptide?

FG loop peptide (FGL) is derived from the neural cell adhesion molecule (NCAM). NCAM is a glycoprotein (a protein that has sugar attached to it) and is found on the surface of nerve cells (neurons) and glial cells (protect neurons). Research shows that NCAM activates FGL which in turn stimulates the production of new projections of developing neurons. FGL also plays an integral role in the formation of synapses between neurons and the proliferation of stem cells – both of these important mechanisms enhance cognitive capacities and protect against stroke and other chronic, debilitating brain diseases.

How FG Loop Peptide Works?

FG loop peptide works by mobilizing the neural stem cells, which have the potential to give rise to offspring cells that grow and develop into neurons (nerve cells) and glial cells. They provide a protective covering to the cells and enhance the transmission of signals, thus improving regenerative capacity and cognitive function.

Chemical Structure of FG Loop Peptide

Research on FG Loop Peptide

Treats Stroke and Traumatic Brain Injuries

FGL can help treat brain damage associated with stroke. There’s an overwhelming body of clinical evidence supporting the regenerative properties of this powerful peptide:

1. A 2008 study published in the Neuroscience Letters found that adolescent rats with a traumatic brain injury that were treated with FGL had reduced inflammatory markers and regulators of programmed cell death (apoptosis). [1]
2. A 2014 study published in the Stem Cells and Reviews showed that exposure of neural stem cells (generate neurons of the central nervous system) to various concentrations of FGL enhanced the proliferation of the stem cells and that injection of FGL in adult rats increased the mobilization of stem cells in different areas of the brain, suggesting that the treatment can be a potential therapeutic option for demyelinating neurological disorders (any condition that damages the protective covering of nerve fibers in the brain). [2]
3. A 2018 study published in the Neurochemical Research that reviewed various preclinical studies on FGL found that the peptide has successfully treated neurological disorders including stroke, traumatic brain injury, and Alzheimer’s disease. [3]
4. In primary rat neurons, FGL induced growth and survival of brain neurons. [4]
5. A cell study found that FGL treatment protected mouse brain cells against lipopolysaccharide-induced changes by reducing the levels of inflammatory markers. [5]
6. In oxygen-deprived rat brain neurons, 24-hour pretreatment with a single injection of FGL significantly protected the neurons against death, suggesting that the peptide can protect against stroke. [6]
7. In a rat model of Alzheimer’s disease, systemic treatment with FGL alleviated the loss of brain neurons. [7]
8. A 2016 study published in the Journal of Neuroimmune Pharmacology found that FGL promotes the regenerative capacity of brain neurons by amplifying remyelination (formation of protective covering around neurons) and modulating inflammation. [8]
9. A cell study also found that FGL promotes the growth and recovery of brain neurons by activating the fibroblast growth factor receptor (FGFR). [9-10]
10. In mice, repeated administration of FGL enhanced the survival of the newly born neurons. [11]
11. In an animal model of stroke, nose-to-brain delivery of FGL prevented brain damage induced by low oxygen levels. [12]

Improves Cognitive Function

Because FGL plays an integral role in the formation of synapses between neurons and proliferation of stem cells, administration of this peptide can help improve different cognitive skills:

1. A cell study found that FGL improved cognitive health by promoting the formation of new brain neurons (neurogenesis). [13]
2. In newborn rats, the administration of FGL through the nose promoted early sensorimotor development and enhanced social memory retention. [14]
3. In rats, FGL treatment ameliorated the working memory deficits induced by phencyclidine. [15]
4. In aged rat brains, FGL treatment ameliorated different processes related to brain aging. [16]
5. When injected at a dose of 8 mg/kg, FGL induced positive changes in the structure of neurons in aged rats. [17]
6. In rats, injection of FGL significantly reduced Abeta25-35-induced cognitive impairment. [18]
7. A cell study found that treatment of rat brain cells with FGL prevented the death of brain neurons. [19]
8. A study also found that FGL has the ability to stimulate the growth of brain neurons. [20]
9. In wild-type rats, FGL treatment improved memory by enhancing the transmission of nerve signals. [21]
10. Studies in animal models of chronic stress have shown that FGL enhances memory by protecting brain neurons. [22-23]
11. A study found that FGL protected against neuroinflammation. [24]
12. FGL has also been found to prevent age-related structural changes in synapses. [25]

Wards Off Depression

There’s also a good deal of evidence supporting the antidepressant properties of FGL, suggesting that this peptide can help correct depressive symptoms and improve quality of life:

1. In mice, acute or repeated administration of FGL reversed depression-like behaviors. [26]
2. A study found that the levels of neural cell adhesion molecules were decreased in patients with depression, suggesting that FGL treatment has the potential to treat depressive symptoms. [27]
3. By improving the function of synapses, FGL can provide a long-term antidepressant effect. [28]
4. In mice, partial reduction in neural cell adhesion molecule induced depression-related behavior. [29]
5. A study found that FGL exerts its antidepressant effects by promoting the growth of new neurons, the development of dendritic spines, and synaptic adaptations. [30]

Fights Inflammation

Evidence also suggests that this NCAM can help fight a wide array of inflammatory conditions through its potent anti-inflammatory properties:

1. A 2010 study published in the Neurobiology of Aging found that administration of FGL in aged rats significantly reduced the increase in pro-inflammatory interleukin-1beta (IL-1beta). [31]
2. A 2009 study published in the Journal of Neurochemistry reported that FGL exerts its anti-inflammatory properties via IGF-1, interferon-gamma, and interferon‐γ modulation. [32-33]
3. A 2017 study published in the Journal of Translational Medicine found that FGL and other anti-inflammatory peptides have the potential to treat various inflammatory diseases such as Alzheimer’s disease and rheumatoid arthritis. [34]
4. A 2006 study published in the Journal of Immunology found that FGL fights inflammation by regulating the development of the immune system cell alpha beta T cells. [35]

Associated Side Effects of FG Loop Peptide

FG loop peptide side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on FG loop peptide. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of FG loop peptide. Despite this, it was listed as a side effect associated with FG loop peptide even though these associated side effects are very uncommon.

Side effects associated with FG loop peptide may include the following:

• Dizziness
• Headache
• Vomiting

References

1. Pedersen MV, Helweg-larsen RB, Nielsen FC, Berezin V, Bock E, Penkowa M. The synthetic NCAM-derived peptide, FGL, modulates the transcriptional response to traumatic brain injury. NeurosciLett. 2008;437(2):148-53.
2. Klein R, Blaschke S, Neumaier B, et al. The synthetic NCAM mimetic peptide FGL mobilizes neural stem cells in vitro and in vivo. Stem Cell Rev Rep. 2014;10(4):539-47.
3. Chu C, Gao Y, Lan X, Thomas A, Li S. NCAM Mimetic Peptides: Potential Therapeutic Target for Neurological Disorders. Neurochem Res. 2018;43(9):1714-1722.
4. Neiiendam JL, Kohler LB, Christensen C, et al. An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons. J Neurochem. 2004;91(4):920-35.
5. Cox FF, Berezin V, Bock E, Lynch MA. The neural cell adhesion molecule-derived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner. Neuroscience. 2013;235:141-8.
6. Skibo GG, Lushnikova IV, Voronin KY, et al. A synthetic NCAM-derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo. Eur J Neurosci. 2005;22(7):1589-96.
7. Corbett NJ, Gabbott PL, Klementiev B, et al. Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimetic peptide. PLoS ONE. 2013;8(8):e71479.
8. Klein R, Mahlberg N, Ohren M, et al. The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke. J NeuroimmunePharmacol. 2016;11(4):708-720.
9. Chen Y, Li S, Berezin V, Bock E. The fibroblast growth factor receptor (FGFR) agonist FGF1 and the neural cell adhesion molecule-derived peptide FGL activate FGFR substrate 2alpha differently. J Neurosci Res. 2010;88(9):1882-9.
10. Aonurm-helm A, Berezin V, Bock E, Zharkovsky A. NCAM-mimetic, FGL peptide, restores disrupted fibroblast growth factor receptor (FGFR) phosphorylation and FGFR mediated signaling in neural cell adhesion molecule (NCAM)-deficient mice. Brain Res. 2010;1309:1-8.
11. Aonurm-helm A, Jurgenson M, Zharkovsky T, et al. Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL. Eur J Neurosci. 2008;28(8):1618-28.
12. Kim YS, Sung DK, Kim H, Kong WH, Kim YE, Hahn SK. Nose-to-brain delivery of hyaluronate – FG loop peptide conjugate for non-invasive hypoxic-ischemic encephalopathy therapy. J Control Release. 2019;307:76-89.
13. Dallérac G, Zerwas M, Novikova T, et al. The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo. Learn Mem. 2011;18(5):306-13.
14. Secher T, Novitskaia V, Berezin V, Bock E, Glenthøj B, Klementiev B. A neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention. Neuroscience. 2006;141(3):1289-99.
15. Secher T, Berezin V, Bock E, Glenthøj B. Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats. Behav Brain Res. 2009;199(2):288-97.
16. Ojo B, Rezaie P, Gabbott PL, et al. A neural cell adhesion molecule-derived peptide, FGL, attenuates glial cell activation in the aged hippocampus. Exp Neurol. 2011;232(2):318-28.
17. Popov VI, Medvedev NI, Kraev IV, et al. A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study. Eur J Neurosci. 2008;27(2):301-14.
18. Klementiev B, Novikova T, Novitskaya V, et al. A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35. Neuroscience. 2007;145(1):209-24.
19. Dityatev A, Dityateva G, Schachner M. Synaptic strength as a function of post- versus presynaptic expression of the neural cell adhesion molecule NCAM. Neuron. 2000;26(1):207-17.
20. Kiselyov VV, Skladchikova G, Hinsby AM, et al. Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure. 2003;11(6):691-701.
21. Cambon K, Hansen SM, Venero C, Herrero AI, Skibo G, Berezin V, Bock E, Sandi C. A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci. 2004 Apr 28;24(17):4197-204.
22. Borcel E, Pérez-Alvarez L, Herrero AI, Brionne T, Varea E, Berezin V, Bock E, Sandi C, Venero C. Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule. BehavPharmacol. 2008 Feb;19(1):41-9.
23. Bisaz R, Schachner M, Sandi C. Causal evidence for the involvement of the neural cell adhesion molecule, NCAM, in chronic stress-induced cognitive impairments. Hippocampus. 2011 Jan;21(1):56-71.
24. Downer EJ, Cowley TR, Cox F, Maher FO, Berezin V, Bock E, Lynch MA. A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation. J Neurochem. 2009 Jun;109(5):1516-25.
25. Ojo B, Rezaie P, Gabbott PL, Davies H, Colyer F, Cowley TR, Lynch M, Stewart MG. Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL. Brain Behav Immun. 2011 Oct 2.
26. Aonurm-helm A, Jurgenson M, Zharkovsky T, et al. Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL. Eur J Neurosci. 2008;28(8):1618-28.
27. Jorgensen OS. Neural cell adhesion molecule (NCAM) and prealbumin in cerebrospinal fluid from depressed patients. ActaPsychiatrScand Suppl. 1988;345:29-37.
28. Muller D, Wang C, Skibo G, et al. PSA-NCAM is required for activity-induced synaptic plasticity. Neuron. 1996;17(3):413-22.
29. Jurgenson M, Aonurm-helm A, Zharkovsky A. Partial reduction in neural cell adhesion molecule (NCAM) in heterozygous mice induces depression-related behaviour without cognitive impairment. Brain Res. 2012;1447:106-18.
30. Steven R. Wainwright and Liisa A. M. Galea, “The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus,” Neural Plasticity, vol. 2013, Article ID 805497, 14 pages, 2013. https://doi.org/10.1155/2013/805497.
31. Downer EJ, Cowley TR, Lyons A, et al. A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL. Neurobiol Aging. 2010;31(1):118-28.
32. Downer EJ, Cowley TR, Cox F, et al. A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation. J Neurochem. 2009;109(5):1516-25.
33. Downer EJ, Cowley TR, Cox F, et al. A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation. J Neurochem. 2009;109(5):1516-25.
34. Gupta S, Sharma AK, Shastri V, Madhu MK, Sharma VK. Prediction of anti-inflammatory proteins/peptides: an insilico approach. J Transl Med. 2017;15(1):7. Published 2017 Jan 6. doi:10.1186/s12967-016-1103-6.
35. Touma M, Chang HC, Sasada T, Handley M, Clayton LK, Reinherz EL. The TCR C beta FG loop regulates alpha beta T cell development. J Immunol. 2006;176(11):6812-23.