Adult neurogenesis and synaptogenesis research peptides
Dihexa, FGL, and the broader research effort to develop small-molecule agonists of the pathways that drive adult neural plasticity.
The discovery that the adult mammalian brain retains some capacity for neurogenesis and substantial capacity for synaptogenesis transformed cognitive-pharmacology research. If new synapses can form throughout life, and if the molecular triggers can be identified, then small-molecule agonists of those pathways become a coherent therapeutic strategy.
Two pathways have dominated the resulting research peptide literature. HGF/c-Met signalling, principally explored through Dihexa, drives dendritic spine formation at picomolar concentrations in published work. FGFR1 signalling, principally explored through the NCAM-mimetic FGL peptide, drives neurite outgrowth and synapse formation. Both pathways converge downstream on PI3K-Akt and MAPK signalling cascades that overlap with BDNF-mediated plasticity.
The strength of these compounds is mechanistic specificity. Unlike the broad BDNF inducers, Dihexa and FGL act on defined receptors with well-characterised downstream signalling. The weakness is the corresponding theoretical safety concern: c-Met and FGFR1 are both involved in oncogenic signalling when chronically activated, and the long-term implications of sustained pharmacological agonism are not characterised in the available literature.
The current state of the field is therefore preclinical: strong mechanistic data, no completed human trials of either compound, and unresolved safety questions that bear directly on whether these compounds will progress to clinical research.