Proneurotrophin (pro-NT)

Proneurotrophins are the unprocessed precursors of mature neurotrophins, including pro-nerve growth factor (pro-NGF), pro-brain-derived neurotrophic factor (pro-BDNF), pro-neurotrophin-3 (pro-NT3), and pro-neurotrophin-4 (pro-NT4). While mature neurotrophins typically promote neuronal survival and differentiation through Trk receptors, proneurotrophins preferentially bind to a heteromeric receptor complex consisting of the p75 neurotrophin receptor (p75NTR) and sortilin to induce programmed cell death (apoptosis) and axonal retraction (Nykjaer et al., 2004, Nature 427:843-848; Lee et al., 2001, Science 294:1945-1948). In the healthy brain, the balance between pro- and mature neurotrophins is tightly regulated; however, in pathological states such as Alzheimer's disease, spinal cord injury, and chronic pain, pro-NGF levels are significantly elevated, contributing to neurodegeneration and hypersensitivity (Fahnestock et al., 2001, Mol Cell Neurosci 18:210-220; Iulita & Cuello, 2014, Trends Pharmacol Sci 35:338-355). Therapeutic strategies targeting proneurotrophins involve monoclonal antibodies designed to neutralize the pro-forms or prevent their binding to the p75NTR/sortilin complex, thereby shifting the balance toward survival-promoting mature neurotrophin signaling (Bruno & Cuello, 2006, J Neurosci 26:8312-8320). These targets are particularly relevant in neurodegenerative conditions where the accumulation of pro-NGF is linked to cholinergic neuron loss and cognitive decline (Capsoni et al., 2011, J Alzheimers Dis 25:43-58).

Other names

Pro-nerve growth factorPro-brain-derived neurotrophic factorPro-neurotrophin-3Pro-neurotrophin-4/5pro-NGFpro-BDNFpro-NT3pro-NT4Precursor neurotrophin

Neutralization of proneurotrophins to prevent binding to the p75NTR/sortilin receptor complex, thereby inhibiting pro-apoptotic signaling and promoting neuronal survival.