Low-affinity nerve growth factor receptor (p75NTR) (NGFR)

The low-affinity nerve growth factor receptor (p75NTR) is a member of the tumor necrosis factor receptor superfamily that plays a dual role in the life and death of neurons. It binds all mature neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), with similar affinity, while binding pro-neurotrophins with high affinity (UniProt P08138). Unlike the Trk family of high-affinity receptors, p75NTR lacks intrinsic tyrosine kinase activity and instead signals through the recruitment of various intracellular adapter proteins (NCBI Gene ID: 4803). Its biological effects are highly context-specific, as it can enhance the survival-promoting effects of Trk receptors or trigger programmed cell death when associated with the co-receptor sortilin (PubMed PMID: 24657964). In pathological conditions, p75NTR is significantly upregulated after neuronal injury and is linked to neurodegeneration in Alzheimer's disease and amyotrophic lateral sclerosis (ALS) (PubMed PMID: 31435140). The receptor also serves as a marker for cancer stem cells, particularly CD271 in melanoma, where it may contribute to tumor progression and metastasis (PubMed PMID: 25605371). Therapeutic strategies targeting p75NTR include small molecule modulators like LM11A-31, which aim to provide neuroprotection by mimicking the beneficial effects of neurotrophin binding. Due to its involvement in both survival and apoptotic pathways, p75NTR remains a complex but promising target for treating diverse neurological and oncological disorders.

Other names

p75 neurotrophin receptorTNFRSF16CD271p75NTRNerve growth factor receptorGp80-LNGFRLow-affinity neurotrophin receptor

Modulates neurotrophin signaling by acting as a co-receptor for Trk receptors to promote survival or partnering with sortilin to induce apoptosis via pro-neurotrophin binding.