FGL

Mechanism (as reported)

In provided studies, FGL has been described as a NCAM mimetic peptide that binds to FGFR-1 and facilitates hippocampal long-term potentiation (LTP) in vivo; anti-inflammatory effects have been associated with CD200 and IL-4/ERK signaling in glial/neuron systems. Another provided report describes distinct receptor mediation for NSC differentiation outcomes after FGL exposure.

Key findings (each cites a source)

• A study reported that FGL facilitates the induction and maintenance of long-term potentiation (LTP) in the dentate gyrus in vivo, without altering basal synaptic transmission at perforant path–dentate gyrus synapses, and it also modified heterosynaptic plasticity at neighboring synapses. [PMID 21508096]
• A study reported that FGL intracerebroventricular infusion in awake animals confirmed its facilitating effect on LTP for up to 24 hours. [PMID 21508096]
• Research investigated whether FGL influences neurogenesis associated with LTP, and reported that their data suggested FGL could alter neurogenesis linked to LTP. [PMID 21508096]
• A study reported that FGL attenuates LPS-induced changes in glial activation markers and pro-inflammatory cytokines in a CD200-dependent manner, with stronger LPS effects and loss of FGL attenuation observed in CD200-deficient cells. [PMID 23337536]
• A study reported that FGL acts as an anti-inflammatory agent in aged rats, attenuating increased markers of activated microglia, increased IL-1beta expression, and impairment in long-term potentiation (LTP). [PMID 18468731]
• A study reported that in the context of FGL anti-inflammatory effects, neuronal CD200 expression was decreased with age and suggested FGL’s suppression of microglial activation was linked to stimulation of neuronal CD200. [PMID 18468731]
• A study reported that FGL enhanced IL-4 release from glial cells and that IL-4 enhanced neuronal CD200 in vitro, with the CD200 increase described as reliant on IL-4-induced ERK signaling. [PMID 18468731]
• Research investigated the biocompatibility of self-assembled FGL peptide nanofibers (FGL-PA) with neural stem cells in vitro and reported that FGL-PA formed a nano-fiber gel and promoted NSC proliferation at certain tested concentrations, with reported changes in differentiation toward neurons under differentiation conditions. [PMID 19068609]
• A study reported that FGL mobilizes NSCs, with FGL increasing NSC proliferation in vitro and increasing proliferative activity in vivo in the subventricular zone (SVZ), supported by PET imaging using [(18)F]-fluoro-L-thymidine. [PMID 24817672]
• A study reported that during differentiation, NCAM promoted neurogenesis whereas FGL induced an oligodendroglial phenotype, and that astrocytic differentiation was neither affected by NCAM nor FGL; the differentiation effects were described as mediated through different receptors. [PMID 24817672]
• An overview/review article reported that FGL improves cognition in laboratory rodents by activating the PKC pathway that triggers activity-dependent delivery of AMPA receptors to synapses. [PMID 29030286]
• A review article also described FGL as a peptide derived from NCAM and associated it with cognitive effects through synaptic functional changes. [PMID 29030286]