Abstract: The present invention relates generally to novel stable pro nerve growth factors (proNGFs) that are stable towards proteolysis by proteases such as furin, PACE4, and PC2. The novel proNGF molecules are prepared with multiple mutations at all the three major processing sites of the pro domain of the natural proNGF molecules. The present invention further discloses the construction, stable expression in insect cells, and purification of stable mutated proNGF molecules. These novel stable proNGF molecules are useful as a reagent to study the physiological process of apoptosis of neuronal cells. Clinically, the stable proNGF molecules, or further mutants derived from them, have potential use in treating certain cancers such as neuroblastoma, pancreatic and breast cancer as well as used as a target in developing other therapeutic agents for neurodegenerative disorders.