Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9NQC3 (Nogo)
 1,062 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amblyopia is difficult to cure in adult due to the declination of visual cortical plasticity with age. However, the mechanisms limiting adult cortical plasticity are still unclear. Inhibition factors associated with myelin are suggested to be crucial for the ocular dominance plasticity in the visual cortex. We hypothesize that blocking Nogo-NgR system with NEP1-40 in adult visual cortex will reactivate the structural and functional plasticity. To back up this hypothesis, we subjected postnatal day 21 (P21) rats to monocular deprivation (MD) model until P45. Then the deprived eyes of MD model rats were reopened and followed by NEP1-40 or PBS administration for 7days. Dendritic spine densities, ultrastructral modifications of synaptic junctions and objective visual function were examined at P52 to determine the therapeutic effects of NEP1-40. Our findings suggest a new curative role for NEP1-40 in structural and functional recovery from the deficits of adult MD rats, and offer a potential therapeutic tool for curing amblyopia and other cortically based visual disorders.
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PMID:Reactivation of visual cortical plasticity by NEP1-40 from early monocular deprivation in adult rats. 2139 58

The p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily, is required as a co-receptor for the Nogo receptor (NgR) to mediate the activity of myelin-associated inhibitors such as Nogo, MAG, and OMgp. p45/NRH2/PLAIDD is a p75 homologue and contains a death domain (DD). Here we report that p45 markedly interferes with the function of p75 as a co-receptor for NgR. P45 forms heterodimers with p75 and thereby blocks RhoA activation and inhibition of neurite outgrowth induced by myelin-associated inhibitors. p45 binds p75 through both its transmembrane (TM) domain and DD. To understand the underlying mechanisms, we have determined the three-dimensional NMR solution structure of the intracellular domain of p45 and characterized its interaction with p75. We have identified the residues involved in such interaction by NMR and co-immunoprecipitation. The DD of p45 binds the DD of p75 by electrostatic interactions. In addition, previous reports suggested that Cys257 in the p75 TM domain is required for signaling. We found that the interaction of the cysteine 58 of p45 with the cysteine 257 of p75 within the TM domain is necessary for p45-p75 heterodimerization. These results suggest a mechanism involving both the TM domain and the DD of p45 to regulate p75-mediated signaling.
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PMID:Heterodimerization of p45-p75 modulates p75 signaling: structural basis and mechanism of action. 2509 80