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)

We investigated the effect of a single administration of recombinant human erythropoietin (rhEPO) on the preservation of the ventral white matter of rats at 4 weeks after contusive spinal cord injury (SCI), a time at which functional recovery is significantly improved in comparison to the controls [Gorio A, Necati Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, Cichetti C, Di Giulio AM, Enver Vardar E, Cerami A, Brines M (2002) Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci U S A 99:9450-9455; Gorio A, Madaschi L, Di Stefano B, Carelli S, Di Giulio AM, De Biasi S, Coleman T, Cerami A, Brines M (2005) Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury. Proc Natl Acad Sci U S A 102:16379-16384]. Specifically, we examined, by morphological and cytochemical methods combined with light, confocal and electron microscopy, i) myelin preservation, ii) activation of adult oligodendrocyte progenitors (OPCs) identified for the expression of NG2 transmembrane proteoglycan, iii) changes in the amount of the chondroitin sulfate proteoglycans neurocan, versican and phosphacan and of their glycosaminoglycan component labeled with Wisteria floribunda lectin, and iv) ventral horn density of the serotonergic plexus as a marker of descending motor control axons. Injured rats received either saline or a single dose of rhEPO within 30 min after SCI. The results showed that the significant improvement of functional outcome observed in rhEPO-treated rats was associated with a better preservation of myelin in the ventral white matter. Moreover, the significant increase of both the number of NG2-positive OPCs and the labeling for Nogo-A, a marker of differentiated oligodendrocytes, suggested that rhEPO treatment could result in the generation of new myelinating oligodendrocytes. Sparing of fiber tracts in the ventral white matter was confirmed by the increased density of the serotonergic plexus around motor neurons. As for chondroitin sulfate proteoglycans, only phosphacan, increased in saline-treated rats, returned to normal levels in rhEPO group, probably reflecting a better maintenance of glial-axolemmal relationships along nerve fibers. In conclusion, this investigation expands previous studies supporting the pleiotropic neuroprotective effect of rhEPO on secondary degenerative response and its therapeutic potential for the treatment of SCI and confirms that the preservation of the ventral white matter, which contains descending motor pathways, may be critical for limiting functional deficit.
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PMID:Erythropoietin-mediated preservation of the white matter in rat spinal cord injury. 1714 61

Unlike mammals, fish are able to regenerate axons in their central nervous system. This difference has been partly attributed to the loss/acquisition of inhibitory proteins during evolution. Nogo-A--the longest isoform of the reticulon4 (rtn4) gene product--is commonly found in mammalian myelin where it acts as a potent inhibitor of axonal regeneration. Interestingly, fish RTN4 isoforms were previously reported to lack the most inhibitory Nogo-A-specific region (NSR). Nevertheless, fish axons collapse on contact with mammalian NSR, suggesting that fish possess a functional Nogo-A receptor but not its ligand. To reconcile these findings, we revisited the early evolution of rtn4. Mining of current genome databases established the unequivocal presence of NSR-coding sequences in fish rtn4 paralogues. Further comparative analyses indicate that the common ancestor of fish and tetrapods had an NSR-coding rtn4 gene, which underwent duplication and divergent evolution in bony fish. Our genomic survey also revealed that the cephalochordate Branchiostoma floridae contains a single rtn gene lacking the NSR. Hence, Nogo-A most probably arose independently in the rtn4 gene of a gnathostome ancestor before the split of the fish and tetrapod lineages. Close examination of the NSR uncovered clusters of structural and sequential similarities with neurocan (NCAN), an inhibitory proteoglycan of the glial scar. Notably, the shared presence of transposable elements in ncan and rtn4 genes suggests that Nogo-A originated via insertion of an ncan-like sequence into the rtn4 gene of an early jawed vertebrate with myelinated axons.
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PMID:Origin of Nogo-A by domain shuffling in an early jawed vertebrate. 2109

Changes in expression of neurorepair and neuroregenerative factors were examined after transient cerebral ischemia in relation to the effects of tissue plasminogen activator (tPA) and the free radical scavenger edaravone. Physiological saline or edaravone was injected twice during 90 min of transient middle cerebral artery occlusion (tMCAO) in rats, followed by the same saline or tPA at reperfusion. Sizes of the infarct and protein factors relating to neurorepair and neuroregeneration were examined at 4d after tMCAO. The protein factors examined were: a chondroitin sulfate proteoglycan neurocan, semaphorin type 3A (Sema3A), a myelin-associated glycoprotein receptor (Nogo receptor, Nogo-R), a synaptic regenerative factor (growth associated protein-43, GAP43), and a chemotropic factor netrin receptor (deleted in colorectal cancer, DCC). Two groups treated by edaravone only or edaravone plus tPA showed a reduction in infarct volume compared to the two groups treated by vehicle only or vehicle plus tPA. Immunohistochemistry and western blot analyses indicated that protein expression of neurocan, Sema3A, Nogo-R, GAP43, and DCC was decreased with tPA, but recovered with edaravone. Additive edaravone prevented the reductions of these five proteins induced by tPA. The present study demonstrates for the first time that exogenous tPA reduced protein factors involved in inhibiting and promoting axonal growth, but that edaravone ameliorated such damage in brain repair after acute ischemia.
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PMID:Modifying neurorepair and neuroregenerative factors with tPA and edaravone after transient middle cerebral artery occlusion in rat brain. 2222 36