Pro-nerve growth factor (proNGF) (proNGF)

Pro-nerve growth factor (proNGF) is the precursor form of nerve growth factor (NGF), a critical neurotrophin involved in the development and maintenance of the nervous system [4.3.1, 4.4.1]. While mature NGF primarily promotes neuronal survival and differentiation through the TrkA receptor, proNGF acts as a distinct signaling ligand that often mediates opposing biological effects [4.3.4, 5.4.1]. It binds with high affinity to a receptor complex composed of the p75 neurotrophin receptor (p75NTR) and sortilin, triggering apoptotic pathways and contributing to neurodegeneration [4.3.2, 5.2.3]. In pathological states such as Alzheimer's disease and spinal cord injury, proNGF levels are significantly elevated, leading to neuronal loss and cognitive decline [4.2.2, 5.4.4]. Beyond the nervous system, proNGF is overexpressed in various cancers, including thyroid and breast cancer, where it promotes tumor cell invasion and metastasis [4.1.2, 4.2.1]. Therapeutic strategies targeting proNGF include neutralizing antibodies and small-molecule modulators of its receptor interactions, aimed at preventing its pro-apoptotic and pro-tumorigenic activities while sparing the beneficial effects of mature NGF [4.3.3, 6.2.3, 6.3.5].

Other names

Nerve growth factor precursorpro-NGFpro-beta-NGFpro-beta-nerve growth factor

Pro-nerve growth factor (proNGF) acts as a signaling ligand by binding to a heteromeric receptor complex consisting of the p75 neurotrophin receptor (p75NTR) and sortilin [4.3.1, 5.2.3]. The pro-domain of proNGF specifically interacts with sortilin, while the mature domain binds to p75NTR [4.3.2, 5.2.2]. This ternary complex triggers pro-apoptotic signaling pathways, such as JNK activation and caspase-dependent cell death, and can suppress survival signaling (e.g., Akt) mediated by mature NGF and TrkA [5.2.1, 5.2.5]. In certain cancers, proNGF can also interact with TrkA and sortilin to promote cell migration and invasion [4.2.1, 6.4.5].