Disease relevance of Ngfr

• In addition, hypothyroidism significantly elevated the levels of 53-kDa pro-nerve growth factor (P < 0.001) and p75 neurotrophin receptor (P < 0.001) and decreased TrkA expression [1].
• We have examined the effect of global transient cerebral ischemia, evoked in rat by 10 min of cardiac arrest, upon the changes in the cellular expression of two nerve growth factor (NGF) receptors (TrkA and p75) in the hippocampus [2].
• TACE-induced cleavage of NgR and p75NTR in dorsal root ganglion cultures disinhibits outgrowth and promotes branching of neurites in the presence of inhibitory CNS myelin [3].
• Neurotrophin-induced p75-mediated death is likely to play an important role in mediating neuronal loss consequent to brain injury [4].
• This result suggested that the mutated LNGFR gene is one of the promising candidate genes for hypertension [5].

Psychiatry related information on Ngfr

• Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits [6].
• Thus, ligand-dependent p75NTR regulation of the ceramide pathway mediates survival in certain neurons and may represent an important target for neuroprotective drugs in degenerative diseases involving p75NTR-expressing neurons, such as Alzheimer's disease [7].

High impact information on Ngfr

• The product of the proto-oncogene trk, p140trk, is a tyrosine kinase receptor that has been identified as a signal-transducing receptor for NGF, while the role of the low affinity NGF receptor, p75NGFR, in signal transduction is less clear [8].
• We have isolated mammalian neural crest cells using a monoclonal antibody to the low affinity NGF receptor, and established conditions for the serial propagation of these cells in clonal culture to assess their developmental potential [9].
• Taken together, these results indicate that NGF has the ability to promote cell death in specific cell types through a ligand-dependent signalling mechanism involving the p75 neurotrophin receptor [10].
• Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75 [10].
• The NGF receptor (NGFR) mRNA was found in the Sertoli cells of rat testis [11].

Chemical compound and disease context of Ngfr

• Nerve growth factor (NGF) treatment of rat PC12 pheochromocytoma cells results in an increase in the tyrosine phosphorylation of the NGF receptor, TrkA, leading to differentiation to a neuronal phenotype [12].
• Parallel studies were performed in rat dorsal root ganglion cultures; suramin potentiated neurite outgrowth and activated the NGF receptor on these cells [13].
• Immunolocalization of the LNGFR and the high-affinity component of the NGF receptor, trk (HNGFR) was studied by electron microscopic morphometric analysis on cultured PC12 pheochromocytoma cells, C6 glioma cells and neonatal rat dorsal root ganglia neurons using a double immunogold labeling technique [14].
• Cholesterol biosynthesis and the pro-apoptotic effects of the p75 nerve growth factor receptor in PC12 pheochromocytoma cells [15].
• In dorsal root ganglion (DRG) neurons isolated from p75(-/-) and control mice, 20 ng/ml NGF completely prevented cisplatin-induced death [16].

Biological context of Ngfr

• The mechanisms employed by the p75 neurotrophin receptor (p75NTR) to mediate neurotrophin-dependent apoptosis are poorly defined [17].
• Our results show that NRAGE contributes to p75NTR-dependent cell death and suggest novel functions for MAGE family proteins [17].
• Surprisingly, p75NTR increased, rather than decreased, Akt phosphorylation in a variety of cell types, including human Niemann-Pick fibroblasts, which lack acidic sphingomyelinase activity [18].
• The precursor of BDNF (pro-BDNF) is differentially cleaved in aminoglycoside-deafened cochleae, resulting in a predominant up-regulation of a truncated form of pro-BDNF, which colocalized with p75NTR-expressing SGN fibers [19].
• Nuclear transcription factors c-Jun and cyclic AMP response element-binding protein phosphorylated by p75NTR- and TrkB-activated signal pathways, respectively, also showed a corresponding differential modulation, suggesting an activation of apoptotic pathways, coupled to a loss of pro-survival neurotrophic support [19].

Anatomical context of Ngfr

• Aminoglycoside-induced degeneration of adult spiral ganglion neurons involves differential modulation of tyrosine kinase B and p75 neurotrophin receptor signaling [19].
• Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor [20].
• p75 and TrkA receptor signaling independently regulate amyloid precursor protein mRNA expression, isoform composition, and protein secretion in PC12 cells [21].
• Increased Pro-Nerve Growth Factor and p75 Neurotrophin Receptor Levels in Developing Hypothyroid Rat Cerebral Cortex Are Associated with Enhanced Apoptosis [1].
• Here, we observed that NgR and p75 were colocalized in low-density membrane raft fractions derived from forebrains and cerebella as well as from cerebellar granule cells [22].

Associations of Ngfr with chemical compounds

• The precise mechanism that p75NTR uses to promote cell death is not certain, but one possibility is that p75NTR-dependent ceramide accumulation inhibits phosphatidylinositol 3-kinase-mediated Akt activation [18].
• However, treatment of PC12 cells with C2-ceramide, an analogue of ceramide, the endogenous product produced by the activity of p75NTR-activated sphingomyelinase, mimicked the effects of NGF on cell morphology and stimulation of both APP mRNA levels and APP secretion [21].
• Effect of anti-NGF on ovarian expression of alpha1- and beta2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries [23].
• Here we show that nerve growth factor (NGF) induced a rapid release of glutamate and an increase of Ca2+ in cerebellar neurons through a p75-dependent pathway [24].
• Nerve growth factor-induced glutamate release is via p75 receptor, ceramide, and Ca(2+) from ryanodine receptor in developing cerebellar neurons [24].
• The region of p75 that Kalirin9 binds includes its mastoparan-like fifth helix, which was shown to recruit RhoGDI-RhoA [25].

Physical interactions of Ngfr

• NgR interacted with p75 in lipid rafts [22].
• We found that p75 can directly bind the GTPases Ras and Rho and that the unstimulated p75 inactivates total cellular Ras through a differential influence on the dissociation of GDP and GTP from Ras and an exchange of bound Ras.GDP for free Ras.GTP [26].
• Brain-derived neurotrophic factor and the anti-p75 monoclonal antibody MC192 have been shown to interfere with the binding of nerve growth factor to p75 [27].
• These data are consistent with receptor allosterism, and prompted a search for TrkA/p75NTR complexes in the absence of NGF [28].
• We suggest that BDNF increases production or release of FGF-2 by binding to p75NTR on Müller cells [29].

Regulatory relationships of Ngfr

• The p75NTR is a multifunctional type I membrane protein that promotes neurotrophin-induced neuronal survival and differentiation by forming a heteromeric co-receptor complex with the Trk receptors [30].
• Soluble NgRECD binds all CNS myelin-derived ligands and thus has the potential to act as an inhibitory signalling antagonist, but the role of TROY and its shed ectodomain in growth cone mobility is unknown. siRNA knockdown of p75NTR also inactivates Rho-A and disinhibits NTF-stimulated RGC neurite outgrowth in cultures with added CNS myelin [31].
• Additionally, BDNF was expressed in Pax7+ satellite cells where it colocalized with p75NTR [32].
• Norepinephrine stores were not affected by high salt intake, but tyrosine hydroxylase, and dopamine beta-hydroxylase were elevated in the salt-induced hypertrophied left ventricle in conjunction with increased levels of nerve growth factor and p75 neurotrophin receptor [33].
• These findings identify NRAGE as a p75NTR interactor capable of inducing caspase activation and cell death through a JNK-dependent mitochondrial apoptotic pathway [34].

Other interactions of Ngfr

• When neurons were initially cultured in 10 ng/ml NGF for 5 d, and then 200 ng/ml NGF was added, LNGF receptor, T alpha 1, and TH mRNAs all increased within 48 h [35].
• The Akt kinase plays a crucial role in supporting Trk-dependent cell survival, whereas the p75 neurotrophin receptor (p75NTR) facilitates cellular apoptosis [18].
• Schwann cell-derived factor-induced modulation of the NgR/p75NTR/EGFR axis disinhibits axon growth through CNS myelin in vivo and in vitro [31].
• TrkC, the high-affinity NT-3 receptor, and trkA, the high-affinity NGF receptor, are both expressed from the early OLP through the mature OL stage [36].
• Activation of the mitogen-activated protein kinase pathway through p75NTR: a common mechanism for the neurotrophin family [37].
• We demonstrate that activation of the TrkA receptor upon binding of nerve growth factor (NGF) regulates the metalloprotease-mediated shedding of p75 leaving a membrane-bound p75 C-terminal fragment (p75-CTF) [38].

Analytical, diagnostic and therapeutic context of Ngfr

• Size exclusion chromatography and co-immunoprecipitation analyses revealed that TrkA forms a molecular complex together with either full-length p75 or membrane-tethered C-terminal fragments [30].
• Finally, Western blot analyses were performed to note the neurotrophin receptor status in the neurons (tyrosine kinase receptors [Trks] and p75) [39].
• Expression of the LNGFR gene is known to be regulated both during development and in response to various agents in cell culture [40].
• Differential change in mRNA expression of p75 and Trk neurotrophin receptors in nucleus gracilis after spinal nerve ligation in the rat [41].
• We have studied by immunohistochemistry the expression of the p75 neurotrophin receptor (p75 NTR) in the sensori-motor cortex of P10 and P20 rats exposed to the inhalation of ethanol during the first week of postnatal life [42].

References