Tumor necrosis factor receptor superfamily member 16 (p75NTR) (p75NTR)

The p75 neurotrophin receptor (p75NTR), also known as Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), is a versatile transmembrane receptor that binds all four mammalian neurotrophins (NGF, BDNF, NT-3, and NT-4) and their precursor pro-forms (UniProt, NIH). It is a member of the tumor necrosis factor receptor superfamily and is characterized by an extracellular domain with four cysteine-rich repeats and an intracellular death domain (NIH). Unlike the high-affinity Trk receptors, p75NTR lacks intrinsic catalytic activity and functions as a signaling hub by interacting with various co-receptors, such as TrkA/B/C, sortilin, and the Nogo receptor (NIH). These interactions allow p75NTR to mediate diverse and often opposing cellular outcomes, including neuronal survival, neurite outgrowth, and programmed cell death (apoptosis) (NIH). In the adult nervous system, p75NTR is typically expressed at low levels but is significantly upregulated following injury or in neurodegenerative conditions like Alzheimer's disease and amyotrophic lateral sclerosis (ALS) (NIH, PubMed). Therapeutic development focuses on small molecule modulators, such as LM11A-31, which aim to selectively inhibit degenerative signaling while promoting neuroprotective pathways (NIH, Alzheimer's Drug Discovery Foundation).

Other names

Nerve growth factor receptorNGFRp75 neurotrophin receptorLow-affinity nerve growth factor receptorCD271Gp80-LNGFR

Small molecule modulation of p75NTR signaling to shift from pro-apoptotic to pro-survival pathways; inhibition of p75NTR oligomerization; competition with pro-neurotrophin binding (NIH, Alzheimer's Drug Discovery Foundation).