Neuron-derived neurotrophic factor (NDNF)

Neuron-derived neurotrophic factor (NDNF) is a glycosylated, secreted protein containing fibronectin type III domains, acting primarily as a neurotrophic and angiogenic factor[2]. NDNF is expressed in the nervous system, endothelium, and other tissues; its secretion is increased in hypoxic or ischemic conditions[1][2]. NDNF promotes endothelial cell survival and angiogenesis via activation of the Akt/endothelial nitric oxide synthase (eNOS) signaling pathway, requiring integrin αvβ3 and likely modulating multiple downstream signals[1]. In neurobiology, NDNF modulates neurite outgrowth and migration of gonadotropin-releasing hormone (GnRH) neurons, with loss-of-function mutations causing congenital hypogonadotropic hypogonadism[2]. In cancer, NDNF acts as a tumor suppressor, being downregulated in diseases such as lung adenocarcinoma and renal cell carcinoma, where its loss is associated with increased proliferation, migration, and invasion via promotion of epithelial-mesenchymal transition (EMT)[2]. NDNF also plays a protective role following cardiac ischemia by reducing cardiomyocyte apoptosis and promoting revascularization[1][2]. Its disease associations, biological activities, and evolutionary conservation mark it as an important endogenous modulator and a potential therapeutic target in vascular, neurodevelopmental, and oncological indications[1][2].

Other names

Protein NDNFC4orf31UNQ2748/PRO6487FLJ23191HH25NORDFibronectin type-III domain-containing protein C4orf31

No specific targeted therapeutics described; experimental modulations act via gene overexpression or knockdown affecting Akt/eNOS pathway and inhibiting FGF signaling[1][2].