Nerve growth factor receptor (NGFR) (NGFR)

The Nerve growth factor receptor (NGFR), also known as p75NTR or CD271, is a 75 kDa type I transmembrane glycoprotein and a member of the tumor necrosis factor receptor (TNFR) superfamily. It serves as a low-affinity receptor for all neurotrophins, including NGF, BDNF, NT-3, and NT-4, and a high-affinity receptor for their precursor forms, known as pro-neurotrophins. NGFR is a pleiotropic signaling molecule that regulates a wide array of biological processes, including neuronal survival, apoptosis, and axonal growth, often acting in concert with high-affinity Trk receptors or co-receptors like sortilin. In pathological states, NGFR is implicated in neurodegenerative diseases such as Alzheimer's, where it mediates amyloid-beta-induced toxicity, and in various cancers where it serves as a marker for cancer stem cells and promotes tumor progression. Therapeutic targeting of NGFR is an emerging field, with small molecule modulators like LM11A-31 in clinical trials for Alzheimer's disease and monoclonal antibodies being explored to deplete CD271-positive cancer cells or block pro-apoptotic signaling.

Other names

p75 neurotrophin receptorp75NTRCD271TNFRSF16Low-affinity nerve growth factor receptorGp80-LNGFRTumor necrosis factor receptor superfamily member 16

Drugs targeting NGFR typically act by modulating the balance between pro-survival and pro-apoptotic signaling pathways. Small molecule modulators like LM11A-31 act as p75NTR ligands that selectively activate survival signaling while inhibiting pro-apoptotic pathways. Monoclonal antibodies may block the binding of neurotrophins or amyloid-beta to the receptor, or induce antibody-dependent cell-mediated cytotoxicity (ADCC) against CD271-positive cancer stem cells.