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)

Nogo-A, a myelin-associated neurite outgrowth inhibitory protein, binds with the Ng-R receptor to activate RhoA intracellular signals and inhibit the plasticity after CNS injury. We evaluated the effect of hyperbaric oxygen (HBO) on the expression of Nogo-A, Ng-R, and RhoA after transient global ischemia in a rat 2 vessel occlusion global ischemic model. Male SD rats (n=78) were randomly divided into 13 groups: 1 sham group, 6 groups of global ischemia, and 6 groups of HBO treatment after global ischemia. HBO (3ATA) was applied for 2 hr at 1 hr after global ischemia. Rats were sacrificed at 6, 12, 24, 48, and 96 hr and 7 days. Global ischemia (10 min) produced a marked increase of Nogo-A/B, Nogo-A, Ng-R, and RhoA expression. Immunohistochemistry showed increased Nogo-A/B and Nogo-A located in the myelin sheath of ischemic brain cortex. Ng-R expressed on the surface of neurons and their processes, and RhoA expressed inside the cytoplasm of neurons in ischemic brain. HBO significantly reduced neurological injury, decreased the levels of Nogo-A, Ng-R, and RhoA in ischemic injured cortex (p<0.05).
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PMID:HBO suppresses Nogo-A, Ng-R, or RhoA expression in the cerebral cortex after global ischemia. 1295 Oct 59

A myelin-associated neurite outgrowth inhibitor, Nogo-A, plays a key role in inhibition of axonal regeneration following injury and ischemia in the central nervous system (CNS). Because axonal injury is a pathologic hallmark of multiple sclerosis (MS), we have investigated the expression of Nogo-A and its receptor NgR in four MS and 12 non-MS control brains by immunohistochemistry. Nogo-A expression was markedly upregulated in surviving oligodendrocytes at the edge of chronic active demyelinating lesions of MS and ischemic lesions of acute and old cerebral infarction, whereas NgR expression was greatly enhanced in reactive astrocytes and microglia/macrophages in these lesions when compared with their expression in the brains of neurologically normal controls. Nogo-A and NgR were also identified in a subpopulation of neurons. In contrast, Nogo-A was undetectable in reactive astrocytes and microglia/macrophages and NgR was not expressed on oligodendrocytes in any cases examined. Western blot analysis and double labeling immunocytochemistry identified the constitutive expression of NgR in cultured human astrocytes. These results suggest that Nogo-A expressed on oligodendrocytes might interact with NgR presented by reactive astrocytes and microglia/macrophages in active demyelinating lesions of MS, although biologic effects caused by Nogo-A/NgR interaction among glial cells remain unknown.
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PMID:Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis. 1575 Dec 27

Nogo-A and its receptor, NgR, have been shown to inhibit neurite growth in the adult rat. Therefore, we hypothesized that Nogo-A and NgR will be upregulated and thus play a similar role in the damage in developing rat brain following hypoxia-ischemia (HI). To test this hypothesis, we subjected postnatal day 7 (P7) rats to HI by permanently ligating the right common carotid artery, followed by exposure to 8%O2/92% N2 for 3 h. Rat brains at 0 h, 6 h, 12 h, 24 h and 72 h after HI, as well as from sham controls, were collected to determine histopathological damage and expression levels of Nogo-A and NgR using hematoxylin and eosin (H&E) staining, immunohistochemistry, fluorescence immunolabeling, Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). We found neuronal degeneration and edema in the ischemic cortex, becoming most prominent at 24 h following HI in this model. Accordingly, the expression of Nogo-A and NgR protein was significantly upregulated at 24 h compared with the sham controls (p<0.01). The upregulated Nogo-A and NgR immunoreactive cells were mainly located in the core of the ischemic cortex and colocalized to neurons. Meanwhile, we found the expression of both Nogo-A and NgR mRNA was increased at 6 h and peaked at 12 h in the ischemic cortex after HI, compared with sham controls. Our findings of upregulation of neurite growth inhibitor Nogo-A and its receptor NgR in ischemic cortex suggest that Nogo-A and NgR may participate in the pathology seen after HI in neonatal rats.
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PMID:Expression of Nogo-A and NgR in the developing rat brain after hypoxia-ischemia. 1692 63

We investigate whether Nogo-A is involved in the secondary axonal degeneration in the thalamus after distal middle cerebral artery occlusion (MCAO) in stroke-prone renovascular hypertensive rats (RHRSP). The expression of Nogo-A in ipsilateral ventroposterior nucleus (VPN) of the thalamus in RHRSP was observed at 1, 2 and 4 weeks after distal MCAO. In addition, intracerebroventricular infusion of NEP1-40, a Nogo-66 receptor (NgR) antagonist peptide, was administered starting 24 h after MCAO and continued for 1, 2 and 4 weeks, respectively. Axonal damage and regeneration were evaluated by analysis of the immunoreactivity (IR) of amyloid betaA4 precursor protein (APP), growth associated protein 43 (GAP-43) and microtubule associated protein 2 (MAP-2) in ipsilateral VPN of the thalamus at 1, 2 and 4 weeks after distal MCAO. Following ischemia, the expression of Nogo-A in oligodendrocytes increased persistently and its localization became redistributed around damaged axons and dendrites. Administration of NEP1-40 downregulated the expression of Nogo-A, reduced axonal injury and enhanced axonal regeneration. Our data suggest that Nogo-A is involved in secondary axonal degeneration and that inhibition of Nogo-A can reduce neuronal damage in the thalamus after distal MCAO.
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PMID:Nogo-A is involved in secondary axonal degeneration of thalamus in hypertensive rats with focal cortical infarction. 1738 69

Ischemic stroke affects many new patients each year. The sequelae of brain ischemia can include lasting sensorimotor and cognitive deficits, which negatively impact quality of life. Currently, treatment options for improving poststroke deficits are limited, and the development of new clinical alternatives to improve functional recovery after stroke is actively under investigation. Anti-Nogo-A immunotherapy to reduce the central nervous system inhibitory environment, cell transplantation strategies, pharmacological agents, and movement-based therapies represent emerging treatments of poststroke deficits through enhancement of neuroanatomical plasticity.
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PMID:Neuronal plasticity and functional recovery after ischemic stroke. 1825 73

This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho-associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.
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PMID:Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. 1898 Apr 76

Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood vessel assembly. Here we show that the reticulon family member 4B, aka Nogo-B, is upregulated in response to ischemia and is necessary for blood flow recovery secondary to ischemia and wound healing. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo. Bone marrow-derived macrophages isolated from Nogo knock-out mice have reduced spreading and chemotaxis due to impaired Rac activation. Bone marrow reconstitution experiments show that Nogo in myeloid cells is necessary to promote macrophage homing and functional recovery after limb ischemia. Thus, endogenous Nogo coordinates macrophage-mediated inflammation with arteriogenesis, wound healing, and blood flow control.
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PMID:Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair. 1980 74

Currently available therapeutics has been less effective in promoting functional recovery from stroke or other injuries in the central nervous system (CNS). Axonal damage is a characteristic pathology seen in CNS injuries. Previously, it was reported that Nogo-A extracellular peptide residues 1-40 (NEP1-40), a competitive antagonist of Nogo-66 receptor (NgR1), has the ability to promote axonal regrowth and functional recovery after CNS injury. However, delivery of the therapeutic proteins into the brain parenchyma is limited due to its inability to cross the blood-brain barrier (BBB). We first generated a biologically active NEP1-40 fusion protein containing the protein transduction domain (PTD) of the transactivator of transcription (TAT), TAT-NEP1-40, which crosses the BBB in vivo after systemic delivery. The TAT-NEP1-40 can protect PC12 cells against oxygen and glucose deprivation (OGD) and promote neurite outgrowth when added exogenously to culture medium. The TAT-NEP1-40 protein transduced into the brain continued to sustain biological activities and protected the brain against ischemia/reperfusion injury through inhibition of neuronal apoptosis. Collectively, our data suggest that TAT-NEP1-40 may be a novel therapeutic candidate for axonal regeneration and functional recovery from CNS injuries such as cerebral hypoxia-ischemia, cerebral hemorrhage, brain trauma, and also for spinal cord injury.
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PMID:TAT-NEP1-40 as a novel therapeutic candidate for axonal regeneration and functional recovery after stroke. 2036 26

For patients with coronary artery disease or limb ischemia, placement of a vein graft as a conduit for a bypass is an important and generally durable strategy among the options for arterial reconstructive surgery. Vein grafts adapt to the arterial environment, and the limited formation of intimal hyperplasia in the vein graft wall is thought to be an important component of successful vein graft adaptation. However, it is also known that abnormal, or uncontrolled, adaptation may lead to abnormal vessel wall remodeling with excessive neointimal hyperplasia, and ultimately vein graft failure and clinical complications. Therefore, understanding the venous-specific pathophysiological and molecular mechanisms of vein graft adaptation are important for clinical vein graft management. Of particular importance, it is currently unknown whether there exist several specific distinct molecular differences in the venous mechanisms of adaptation that are distinct from arterial post-injury responses; in particular, the participation of the venous determinant Eph-B4 and the vascular protective molecule Nogo-B may be involved in mechanisms of vessel remodeling specific to the vein. This review describes (1) venous biology from embryonic development to the mature quiescent state, (2) sequential pathologies of vein graft neointima formation, and (3) novel candidates for strategies of vein graft management. Scientific inquiry into venous-specific adaptation mechanisms will ultimately provide improvements in vein graft clinical outcomes.
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PMID:Mechanisms of vein graft adaptation to the arterial circulation: insights into the neointimal algorithm and management strategies. 2060 26

Nogo-B is a member of the reticulon family of proteins that has been implicated in diverse forms of vascular injury. Although Nogo-B is expressed in renal tissues, its localization and function in the kidney have not been examined. Here, we report that Nogo-B is expressed specifically in the epithelial cells of the distal nephron segments in the murine kidney. After unilateral ureteral obstruction (UUO) and ischemia/reperfusion, Nogo-B gene and protein levels increased dramatically in the kidney. This increase was driven in part by injury-induced de novo expression in proximal tubules. Examination of Nogo-B immunostaining in human biopsy specimens from patients with acute tubular necrosis showed similar increases in Nogo-B in cortical tubules. Mice genetically deficient in Nogo-A/B were indistinguishable from wild-type (WT) mice based on histological appearance and serum analyses. After UUO, there was a significant delay in recruitment of macrophages to the kidney in the Nogo-A/B-deficient mice. However, measurements of fibrosis, inflammatory gene expression, and histological damage were not significantly different from WT mice. Thus, Nogo-B is highly expressed in murine kidneys in response to experimental injuries and may serve as a marker of diverse forms of renal injury in tissues from mice and humans. Furthermore, Nogo-B may regulate macrophage recruitment after UUO, although it does not greatly affect the degree of tissue injury or fibrosis in this model.
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PMID:Identification and regulation of reticulon 4B (Nogo-B) in renal tubular epithelial cells. 2097 39


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