Neuromodulin

Neuromodulin (GAP43) is a 24.8 kDa protein associated with nerve growth and a major component of axonal growth cones, the motile structures at the tips of elongating axons (UniProt: P17677). It plays a role in axonal and dendritic filopodia induction, functioning as a critical regulator of neuronal morphogenesis and plasticity.

GAP43 is expressed in neurons and participates in developmental and regenerative processes in the nervous system. The protein has no curated disease associations in UniProt itself, but has been investigated in neuropathological contexts due to its role in synaptic and axonal integrity.

In Alzheimer's disease, GAP43 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC = −0.484; Chaparral AD proteomics). This reduction was observed in human post-mortem AD brain analyzed by quantitative TMT-labeled proteomics across subcellular fractions (P2, P3, S2, S3), suggesting diminished axonal growth capacity and potential compromise of neuritic integrity in AD pathology.