Netrin-1

Netrin-1 (NTN1) is an axon guidance protein that regulates neuronal migration and outgrowth through interactions with DCC and UNC5 receptors, promoting either attraction or repulsion depending on receptor engagement (UniProt: O95631). Beyond its developmental roles, it functions as a survival factor that inhibits apoptosis and is implicated in tumorigenesis. The protein is primarily involved in commissural axon guidance in the central nervous system and dorsal root ganglion projections.

Netrin-1 is associated with mirror movements 4 (MRMV4), an autosomal dominant disorder characterized by contralateral involuntary mirror movements (UniProt: O95631). Its expression is relevant to neuronal development, axonal dynamics, and cell survival pathways across multiple tissues.

In Alzheimer's disease, Netrin-1 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 1.74 in human post-mortem AD brain proteomics analysis (Chaparral AD proteomics). This upregulation suggests potential involvement in AD-related neuropathological processes, though the functional significance in disease pathogenesis remains to be clarified.