[12] p75NTR is a type I transmembrane protein, with a molecular weight of 75 kDa, determined by glycosylation through both N- and O-linkages in the extracellular domain.
[13] The p75ECD-binding interface to NT-3 can be divided into three main contact sites, two in the case of NGF, that are stabilized by hydrophobic interactions, salt bridges, and hydrogen bonds.
[18][19] Recent research has suggested a number of roles for the LNGFR, including in development of the eyes and sensory neurons,[20][21] and in repair of muscle and nerve damage in adults.
[22][23][24] Two distinct subpopulations of Olfactory ensheathing glia have been identified[25] with high or low cell surface expression of low-affinity nerve growth factor receptor (p75).
[26] When p75NTR initiates apoptosis, NGF binding to Tropomyosin receptor kinase A (TrkA) can negate p75NTR apoptotic effects.
[26] p75NTR functions in a complex with Nogo-66 receptor (NgR1) to mediate RhoA-dependent inhibition of growth of regenerating axons exposed to inhibitory proteins of CNS myelin, such as Nogo, MAG or OMgP.
Ras homolog family member A (RhoA) causes the actin cytoskeleton to become rigid which limits growth cone mobility and inhibits neuronal elongation in the developing nervous system.
[29] Neurotrophin binding to p75NTR activates the c-Jun N-terminal kinases (JNK) signaling pathway causing apoptosis of developing neurons.
[31] In the apoptosis pathway, members of the TNF receptor superfamily assemble a death-inducing signaling complex (DISC) in which TRADD or FADD bind directly to the receptor's death domain, thereby allowing aggregation and activation of Caspase 8 and subsequent activation of the Caspase cascade.
There is increased expression of p75NTR in the hippocampus of Huntington's disease patients (including mice models and humans).
One study using the superoxide dismutase 1 (SOD1) mutant mouse, an ALS model which develops severe neurodegeneration, the expression of p75NTR correlated with the extent of degeneration and p75NTR knockdown delayed disease progression.
AD is a neurodegenerative disease characterized by the loss of cognitive functioning - thinking, remembering and reasoning- and behavioral abilities to such an extent that it interferes with a person's daily life and activities.
The neuropathological hallmarks of AD include amyloid plaques and neurofibrillary tangles, which lead to neuronal death.
[36] In humans with AD, increases in p75NTR expression relative to TrkA have been suggested to be responsible for the loss of cholinergic neurons.
[40] This study also found that NGFR signaling in humans is age-related and correlates with proliferative potential of neural progenitors.
[45][44][46][47] Recently, expression of p75NTR (NGFR) was associated with progressive intracranial disease in melanoma patients [48] Low-affinity nerve growth factor receptor has been shown to interact with: