Growth-associated protein 43 (GAP-43)

Growth-associated protein 43 (GAP-43) is a neuron-specific, membrane-associated phosphoprotein crucial for axonal outgrowth, synaptic plasticity, and neural regeneration. Highly expressed during development and after neuronal injury, GAP-43 is associated with the presynaptic membrane, influencing actin cytoskeleton remodeling, axon guidance, dendrite formation, and memory function. It serves as a substrate for protein kinase C (PKC) and binds calmodulin and phospholipids, functioning as an adaptor protein at nerve terminals. Changes in GAP-43 expression or function have been linked to neurodevelopmental disorders, epilepsy, and neurodegenerative diseases such as Alzheimer’s, where it is also being explored as a biomarker for disease progression and synaptic integrity. GAP-43 mutations or dysregulation result in defective neural connectivity and severe developmental phenotypes.

Other names

protein F1neuromodulinneural phosphoprotein B-50axonal membrane protein GAP-43calmodulin-binding protein P-57nerve growth-related peptide GAP43neuron growth-associated protein 43Basp2pp46

In preclinical models, DHF increases GAP-43 expression, believed to improve neuronal survival and reduce pathology by mimicking BDNF signaling. Drugs targeting PKC can indirectly modulate GAP-43 function through its phosphorylation in neurons.