p75 neurotrophin receptor

Class

p75 neurotrophin receptor modulator

The p75 neurotrophin receptor (p75NTR) is a cell-surface receptor belonging to the tumor necrosis factor receptor superfamily. It binds neurotrophins—including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—as well as their immature precursor forms, called proneurotrophins. Depending on which ligand it binds and which co-receptors are present, p75NTR can promote either neuronal survival and growth or programmed cell death (apoptosis) and synaptic weakening. This dual capacity makes it a plausible target in neurodegenerative and neuropathic conditions, where an imbalance toward the death-promoting signaling contributes to loss of neurons or synaptic connections, as proposed in Alzheimer's disease, amyotrophic lateral sclerosis, and peripheral neuropathies. Rather than simply blocking or activating the receptor outright, small-molecule modulators are designed to bias its signaling toward the survival-supporting branch while dampening the degenerative branch, aiming to preserve neurons and their connections without the side effects seen with direct neurotrophin administration, such as pain sensitization. Because p75NTR also participates in normal processes like nerve myelination and axon pathfinding, therapeutic modulation must be selective enough to correct pathological signaling without disrupting these physiological roles.