FGL

Also known as: Fibroblast Growth Loop, NCAM-derived peptide, Neural cell adhesion molecule peptide

Cognitive & NootropicNeuroprotective

Overview

FGL is a 15-amino acid peptide synthesized from the interconnecting loop region of the second fibronectin type III module in the extracellular domain of the neural cell adhesion molecule (NCAM). It mimics NCAM-fibroblast growth factor receptor 1 (FGFR1) interactions, driving neurotrophic, neuroprotective, and anti-inflammatory effects. Phase I clinical trials have demonstrated safety and acceptable pharmacokinetics after intranasal administration, and it is in clinical development for neurodegenerative diseases.

Mechanism of Action

FGL directly binds NCAM and activates FGFR1 through NCAM-mediated signaling, stimulating downstream cascades governing neuronal survival, cell adhesion, and synaptic stability. This promotes: enhanced long-term potentiation (LTP) in hippocampus and dentate gyrus; neurite outgrowth and axonal regeneration; synaptic plasticity and spinogenesis (aged rat study: significant changes in spine and synapse ultrastructure); and anti-inflammatory effects mediated by increased IL-4 secretion from glial cells, reducing microglia activation and IL-1β production.

Potential Benefits

  • Enhanced LTP in hippocampus and dentate gyrus
  • Improved spatial and working memory in aged models
  • Significant ultrastructural changes in synapses and dendritic spines in aged rats
  • Neuroprotection against amyloid-beta and stress-induced damage
  • Anti-inflammatory effects via IL-4/CD200 pathway
  • Phase I safety established with intranasal delivery
  • Potential for Alzheimer's disease, stroke, and TBI applications

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

Phase I: intranasal administration; dose escalation from 2-50 mg confirmed tolerability. Preclinical studies: 8-10 mg/kg subcutaneously.

Amino Acid Sequence

Thr-Val-Ser-Lys-Glu-Lys-Glu-Lys-Lys-Glu-Gln-Lys-Lys-Val-Ala (15 amino acids from NCAM FNIII-2 loop)

Side Effects & Safety

  • Well-tolerated in Phase I
  • Preclinical seizure threshold concern noted in epilepsy models at high doses
  • Intranasal delivery with good brain penetration reduces systemic risks

Synergistic Compounds

The following compounds have been studied alongside FGL for potential complementary or synergistic effects:

CerebrolysinP21Semax

Learn More

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References & Further Reading

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