FGL-S 10mg

FGL-S: Overview

Fibroblast growth loop (FGL) is a 15-amino acid synthetic peptide derived from the neural cell adhesion molecule (NCAM). Research indicates that it possesses neurotrophic and memory-enhancing properties, promoting neurite outgrowth, neuron survival, and synaptic growth/plasticity. In animal models, FGL has shown neuroprotective effects including reduced neuron death following stroke, reductions in neuron death in neurodegenerative diseases, and reduced inflammation (via attenuated microglial activation) in the brain and central nervous system. In animal studies, FGL has been found to enhance social memory retention, improve sensorimotor development, and improve cognitive function. FGL comes in several forms including FGL-1, FGL-2 and FGL-S. FGL-S is most similar to FGL-1 in terms of effects, but is a shorter amino acid and as such is easier and more cost effective to produce.

FGL-S: Structure

Source: PubChem

Amino Acid Sequence: H-Glu-Val-Tyr-Val-Val-Ala-Glu-Asn-Gln-Gln-Gly-Lys-Ser-Lys-Ala-OH
Chemical Formula: C₇₁H₁₁₆N₂₀O₂₅
Molecular Weight: 1649.8 g/mol
PubChem CID: 16200289
CAS No: 499993-62-3
Synonyms: HY-P3281, DA-53184, CS-0655069

FGL-S: Research

FGL-S: What is FGL?

FGL, short for fibroblast growth loop, is a mimetic of a section of the second fibronectin type III module of neural cell adhesion molecule (NCAM). That mouthful of a sentence doesn’t do much to clarify what FGL is, however, so let’s break it down.

NCAM, also called CD56, is a binding protein found on the surface of neurons, glia, and skeletal muscle cells. NCAM signals neuron growth via the fibroblast growth factor receptor and regulates interactions between neurons and between neurons and muscle cells. It is thought that NCAM is important for cell-to-cell adhesion and that it influences the connections of neurons with one another and with muscle cells at the neuromuscular junction.

Image showing the location of FGL within the larger second fibronectin type II module of NCAM. The FGL sequence, delineated in yellow, possesses the ability of its parent molecule to stimulate the fibroblast growth factor receptor on neurons and a handful of other cells in the central nervous system.

Source: Wiley Online Library

Research indicates that NCAM is important in neuron growth and synaptic plasticity. This, of course, means the NCAM is important in learning and memory. Studies in animals have shown that NCAM plays an integral role in regeneration of damaged neural tissue[1]. Mice lacking all forms of NCAM show problems with cognitive functions, especially in spatial learning and memory. They also have difficulties with fear-related learning and show impaired long-term potentiation (LTP), a key process for memory formation. Additionally, these mice display depression-like behavior and reduced formation of new neurons in the hippocampus, along with lower levels of activated CREB, a protein important for brain function[2].

As noted above, NCAM works via interaction with fibroblast growth factor receptor (FGFR1 in this case). FGL mimics the binding of NCAM to FGR1, stimulating neurons to increase in length. In short, FGL activates NCAM and thus stimulates the beneficial effects of the fibroblast growth factor receptor on neuron/synaptic growth. Research in animal models indicates that FGL increases the ration of mushroom to thin spines on neurons and that it also increases the number of multivesicular bodies and coated pits. In other words, FGL promotes the growth of dendritic segments and thus improves the interconnection between neurons.

Image showing the increased length of neurons and increased density and robustness of dendrites on neurons treated with FGL.

Source: Wiley Online Library

FGL-S Research Administration

FGL is a large peptide and thus one would expect that its administration would be limited to IV use with perhaps an argument for subcutaneous use. Research in rats, however, indicates that FGL uptake is not only potent following subcutaneous administration, but that it is equally potent following intranasal administration. In both cases, uptake is rapid with FGL detected in the blood just 10 minutes after administration. Additionally, FGL could be detected in blood and cerebrospinal fluid for up to 5 hours following administration[3]. Clearly FGL crosses the blood-brain barrier easily and rapidly, indicating that administration in experimental settings should be relatively straightforward.

It is worth noting that while FGL can be administered as a monomer, multimeric forms of the peptide have higher potency for receptor activation. Dimeric (FGL-2) and tetrameric (FGL-4) forms are most commonly used in research settings due to their high potency. These peptides are, however, exceptionally difficult to manufacture and can thus be prohibitively expensive. FGL-S offers an affordable alternative that preserves most of the potency and benefits of FGL-1 and FGL-2.

Intranasal doses of FGL are well tolerated, with no significant changes seen in ECGs, vital signs, or lab tests. A total of three participants (13%) reported five mild side effects.

FGL-S and Cognitive Function

Research in newborn rats shows that FGL can accelerate early development of coordination skills while research in older rats shows increased retention of social memory. Recall that FGL can stimulate function of the fibroblast growth factor receptor on cells within the central nervous system. This activation leads to changes in a number of intracellular signal transduction pathways such as the Ras-mitogen activated protein kinase and the phosphatidulinositol-3-kinase (PI3K)-Akt pathways. In the research on rats, neuron growth in three different sets of neurons was observed, each showing slightly difference responses due to differing expression of fibroblast growth factor receptor subtypes/isotypes. Although the FGL peptide generally stimulates neurite outgrowth in the neuronal cell types studied, the strength and pattern of the response varies between them.

Dopaminergic neurons