NDNF is evolutionarily well conserved, being present in invertebrate animals. Multiple cysteines are conserved between species and secondary structure prediction shows that NDNF is mainly composed of beta-strands.NDNF is a glycosylated, disulfide-bonded secretory protein that contains a fibronectin type III domain. NDNF promoted migration and growth and elicited neurite outgrowth of mouse hippocampal neurons in culture. NDNF also protected cultured hippocampal neurons against excitotoxicity and amyloid beta-peptide toxicity. NDNF was exclusively expressed in the brain and spinal cord. NDNF was expressed by neurons and not by astrocytes. NDNF expression was observed in the neurons during development.NDNF is a novel neurotrophic factor derived from neurons that may be useful in the treatment of neuronal degeneration diseases and nerve injuries.