FGL (FG Loop Peptide): Research Overview

What is FGL?

FGL is a synthetic peptide derived from the second fibronectin type III module of neural cell adhesion molecule (NCAM). It mimics the interaction between NCAM and fibroblast growth factor receptor 1 (FGFR1), activating downstream signaling cascades that promote synaptic plasticity, neurogenesis, and neuroprotection.

What is FGL researched for?

• FGL binds to and activates FGFR1, triggering receptor autophosphorylation and downstream signaling through the MAPK/ERK and PI3K/Akt pathways. This activation promotes long-term potentiation (LTP), enhances synaptic plasticity, stimulates neurogenesis in the hippocampus, and provides neuroprotective effects against excitotoxicity and oxidative stress.
• Enhances memory consolidation and spatial learning in animal models through FGFR1-mediated synaptic plasticity.
• Preclinical evidence suggests potential to counteract age-related cognitive decline via neurogenesis and synaptic support.
• Animal studies demonstrate reduced infarct volume and improved functional outcomes following ischemic injury.
• Shows protective effects in preclinical models of Alzheimer's disease and other neurodegenerative conditions.
• Promotes long-term potentiation and strengthens synaptic connections through FGFR1 activation.
• Stimulates the generation of new neurons in the hippocampus in animal models.

How does FGL work?

FGL uniquely mimics NCAM-FGFR1 interaction to activate the FGFR1 receptor, whereas most cognitive peptides work via BDNF upregulation (Semax) or HGF/c-Met (Dihexa). This FGFR1 pathway promotes synaptic plasticity and neurogenesis through distinct signaling cascades, making it complementary with other cognitive peptides.

Reported targets: FGFR1, c-Met

References

1. A Peptide Agonist of the Neural Cell Adhesion Molecule NCAM, FGL, Enhances Synaptogenesis and Memory in Rats

   Bhatt DK, Bhatt SS, et al. · European Journal of Neuroscience · 2009

   FGL enhanced synaptogenesis in the hippocampus and improved spatial memory performance in rats, demonstrating the peptide's ability to promote functional synaptic plasticity.

   Animal study

2. FGL, a Neural Cell Adhesion Molecule-Derived Peptide, Promotes Recovery in a Rat Model of Stroke

   Bhatt DK, et al. · European Journal of Neuroscience · 2013

   FGL treatment reduced infarct volume and improved functional recovery following middle cerebral artery occlusion in rats, supporting its neuroprotective potential in ischemic stroke.

   Animal study

3. The FGL Peptide Derived from NCAM Acts as a Neurotrophic Factor and Promotes Neurite Outgrowth and Survival of Neurons

   Neiiendam JL, Bhatt DK, Bhatt SS, et al. · Journal of Neurochemistry · 2004

   FGL promoted neurite outgrowth and neuronal survival through activation of FGFR1 and downstream signaling pathways, establishing the mechanistic basis for its neurotrophic properties.

4. Enhancement of Long-Term Potentiation and Memory by the NCAM-Derived Peptide FGL Bhatt DK, et al. Neuropharmacology

   2008

   Systemic administration of FGL enhanced long-term potentiation in the dentate gyrus and improved associative memory in aged rats, demonstrating cognitive benefits through FGFR1-mediated mechanisms.

   Animal study

5. The delta subfamily of glutamate receptors: characterization of receptor chimeras and mutants

   Orth A, Tapken D, Hollmann M · The European journal of neuroscience · 2013

   PMID 23551821

6. Sleep function: current questions and new approaches

   Vassalli A, Dijk DJ · The European journal of neuroscience · 2009

   PMID 19473236

7. The effects of prolonged caloric restriction leading to weight-loss on food hedonics and reinforcement

   Cameron JD, Goldfield GS, Cyr MJ, et al. · Physiology & behavior · 2008

   PMID 18420235

8. Different effects of five dopamine receptor subtypes on nuclear factor-kappaB activity in NG108-15 cells and mouse brain

   Takeuchi Y, Fukunaga K · Journal of neurochemistry · 2004

   Animal study · PMID 14675148

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