Neudesin neurotrophic factor (NENF) (NENF)

Neudesin neurotrophic factor (NENF), also known as Neudesin, is a secreted protein that functions as a non-canonical neurotrophic factor and a member of the membrane-associated progesterone receptor (MAPR) family. It contains a conserved cytochrome b5-like heme/steroid-binding domain, and its neurotrophic activity is significantly enhanced upon binding to heme. NENF is primarily expressed in the central nervous system, where it promotes neuronal differentiation and survival through the activation of MAPK and PI3K/Akt signaling pathways. Beyond its neural roles, NENF acts as an adipokine that regulates energy metabolism and adipogenesis; its deficiency in mice leads to resistance to diet-induced obesity but also results in increased anxiety-like behavior. In the context of oncology, NENF is frequently overexpressed in various malignancies, including breast, colorectal, and hepatocellular carcinomas, where it drives tumor growth, invasiveness, and metastasis. Consequently, NENF mRNA and protein are being explored as promising therapeutic targets and diagnostic biomarkers for metabolic disorders and cancer.

Other names

NeudesinNeuron-derived neurotrophic factorCIR2SPUFSCIRP10GIG47Cell growth-inhibiting protein 47

Therapeutic strategies targeting NENF mRNA primarily involve RNA interference (RNAi) or antisense oligonucleotides (ASOs) to induce mRNA degradation and suppress protein expression. At the protein level, NENF acts as an extracellular ligand that activates the MAPK/ERK and PI3K/Akt signaling pathways, likely through a Gi/Go protein-coupled receptor mechanism.