Disease relevance of Rtn4r

• However, neurite outgrowth from NgR-deficient postnatal dorsal root ganglion or cerebellar granule neurons is inhibited by myelin and by a Nogo-66 substrate to the same extent as is from wild-type neurons, whereas p75(NTR)-deficient neurons are less inhibited [1].
• Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury [2].
• In the grafted spinal cord, gliosis was inhibited and Nogo receptor expression was scarcely detected [3].

Psychiatry related information on Rtn4r

• In NgR-/- mice, plasticity during the critical period is normal, but it continues abnormally such that ocular dominance at 45 or 120 days postnatal is subject to the same plasticity as at juvenile ages [4].

High impact information on Rtn4r

• Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth [5].
• Cleavage of NgR and other GPI-linked proteins from the cell surface renders axons of dorsal root ganglia insensitive to OMgp [5].
• The Nogo-66 receptor: focusing myelin inhibition of axon regeneration [6].
• New findings implicate NgR as a point of convergence in signal transduction for several myelin-associated inhibitors [6].
• Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury [7].

Biological context of Rtn4r

• The NgR ligand-binding domain promotes neurite outgrowth on Nogo-66, regardless of the genotype of the neurons, indicating that the NgR ligand-binding domain can act independent of NgR [1].
• Subcutaneous treatment with the NgR antagonist peptide NEP1-40 (Nogo extracellular peptide, residues 1-40) results in extensive growth of corticospinal axons, sprouting of serotonergic fibers, upregulation of axonal growth protein SPRR1A (small proline-rich repeat protein 1A), and synapse re-formation [8].
• No significant changes in NgR mRNA levels were observed in jimpy, where the increase in p75 level can be correlated with the cell death of oligodendrocytes [9].
• Additional studies have identified a potential coreceptor for NgR as p75(NTR), and a second-messenger pathway involving RhoA that inhibits neurite elongation [6].

Anatomical context of Rtn4r

• While this suggests a converging role of the p75(NTR)/NgR receptor complex for myelin-derived neurite growth inhibitors, we show here that NgR/p75(NTR) is not required for mediating the inhibitory activity of the two myelin components NiG, unlike Nogo-66 a distinct domain of Nogo-A, and Versican V2 [10].
• Thus, NgR is not essential for mediating inhibitory signals from CNS myelin, at least in the neurons tested, whereas p75(NTR) plays a central role in this response [1].
• Neither NgR-nor p75(NTR)-deficient mice showed enhanced regeneration of corticospinal tract axons in comparison with wild-type controls after spinal dorsal hemisection [1].
• Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury [8].
• DRG neurons lacking NgR do not bind Nogo-66, and their growth cones are not collapsed by Nogo-66 [7].

Associations of Rtn4r with chemical compounds

• We found that Nogo-A and Nogo receptor are differentially regulated after kainic acid or perforant pathway lesions [11].
• For example, NEP1-40 is a synthetic peptide that promotes axonal regeneration by blocking Nogo-66/NgR interaction and chondroitinase ABC (ChABC), which degrades CS, thereby also promoting axon regrowth [12].
• Through site-directed mutagenesis, we demonstrate that the central 15-28 aa of Abeta associate with specific surface-accessible patches on the leucine-rich repeat concave side of the solenoid structure of NgR [13].

Other interactions of Rtn4r

• The p75 receptor (p75(NTR)) binds growth-promoting neurotrophins (NTs) as well as the common receptor for growth-inhibiting myelin-derived proteins (the Nogo receptor) and so is well situated to gauge the balance of positive and negative influences on axonal plasticity [14].
• Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions [11].
• The oligodendrocyte-myelin glycoprotein is a ligand of the neuronal Nogo receptor and a potent inhibitor of neurite outgrowth, but its physiological function remains to be elucidated [15].
• Subcutaneous Nogo receptor removes brain amyloid-beta and improves spatial memory in Alzheimer's transgenic mice [13].

Analytical, diagnostic and therapeutic context of Rtn4r

• The expression of mRNA for Nogo-66 receptor (NgR) in unoperated adult rats and mice, and rats with nerve grafts placed in the thalamus and cerebellum to stimulate axonal regeneration, was investigated by in situ hybridization [16].
• The cells lacked the expression of Nogo receptor that was of great advantage for axon growth after transplantation to an injured spinal cord [3].

References