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nogo receptor

Gabriella Smedfors, Lars Olson, Tobias E Karlsson
An appropriate strength of Nogo-like signaling is important to maintain synaptic homeostasis in the CNS. Disturbances have been associated with schizophrenia, MS and other diseases. Blocking Nogo-like signaling may improve recovery after spinal cord injury, stroke and traumatic brain injury. To understand the interacting roles of an increasing number of ligands, receptors and modulators engaged in Nogo-like signaling, the transcriptional activity of these genes in the same brain areas from birth to old age in the normal brain is needed...
2018: Frontiers in Molecular Neuroscience
Keita Takahashi, Hideyuki Takeuchi, Yuji Kurihara, Hiroshi Doi, Misako Kunii, Kenichi Tanaka, Haruko Nakamura, Ryoko Fukai, Atsuko Tomita-Katsumoto, Mikiko Tada, Yuichi Higashiyama, Hideto Joki, Shigeru Koyano, Kohtaro Takei, Fumiaki Tanaka
BACKGROUND: Although inflammation in the central nervous system is responsible for multiple neurological diseases, the lack of appropriate biomarkers makes it difficult to evaluate inflammatory activities in these diseases. Therefore, a new biomarker reflecting neuroinflammation is required for accurate diagnosis, appropriate therapy, and comprehension of pathogenesis of these neurological disorders. We previously reported that the cerebrospinal fluid (CSF) concentration of lateral olfactory tract usher substance (LOTUS), which promotes axonal growth as a Nogo receptor 1 antagonist, negatively correlates with disease activity in multiple sclerosis, suggesting that variation in LOTUS reflects the inflammatory activities and is a useful biomarker to evaluate the disease activity...
February 17, 2018: Journal of Neuroinflammation
Yutaka Kawakami, Yuji Kurihara, Yu Saito, Yuki Fujita, Toshihide Yamashita, Kohtaro Takei
Nogo receptor type 1 (NgR1) is known to inhibit neuronal regeneration in the CNS. We have previously identified lateral olfactory tract usher substance (LOTUS) interacts with NgR1 and inhibits its function by blocking its ligand binding. Therefore, LOTUS is expected to have therapeutic potential for the promotion of neuronal regeneration. However, it remains unknown whether the soluble form of LOTUS (s-LOTUS) also has an inhibitory action on NgR1 function as a candidate for therapeutic agents. Here, we show that s-LOTUS inhibits NgR1-mediated signaling by inhibiting the molecular interaction between NgR1 and its co-receptor p75 neurotrophin receptor (p75 NTR )...
February 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ying Jin, Wenquan Hu, Tong Liu, Ujala Rana, Irene Aguilera-Barrantes, Amanda Kong, Suresh N Kumar, Bei Wang, Pin Gao, Xiang Wang, Yajun Duan, Aiping Shi, Dong Song, Ming Yang, Sijie Li, Bing Han, Gang Zhao, Zhimin Fan, Qing Robert Miao
Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of estrogen receptor α (ERα) positive breast cancer cases achieve a pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and promotes Ras translocation to the plasma membrane. Here, we demonstrate NgBR as a potential therapeutic target for ERα positive breast cancer patients to attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell apoptosis by modulating expression of p53 and survivin in ERα positive breast cancer cells via NgBR-mediated PI3K/AKT and MAPK/ERK signaling pathways...
January 23, 2018: Cancer Letters
Joshua Holcomb, Maysaa Doughan, Nicholas Spellmon, Brianne Lewis, Emerson Perry, Yingxue Zhang, Lindsey Nico, Junmei Wan, Srinivas Chakravarthy, Weifeng Shang, Qing Miao, Timothy Stemmler, Zhe Yang
The Nogo-B receptor (NgBR) is involved in oncogenic Ras signaling through directly binding to farnesylated Ras. It recruits farnesylated Ras to the non-lipid-raft membrane for interaction with downstream effectors. However, the cytosolic domain of NgBR itself is only partially folded. The lack of several conserved secondary structural elements makes this domain unlikely to form a complete farnesyl binding pocket. We find that inclusion of the extracellular and transmembrane domains that contain additional conserved residues to the cytosolic region results in a well folded protein with a similar size and shape to the E...
2018: PloS One
Gwangho Yoon, Shahid Ali Shah, Tahir Ali, Myeong Ok Kim
Alzheimer's disease is a major neurodegenerative disease characterized by memory loss and cognitive deficits. Recently, we reported that osmotin, which is a homolog of adiponectin, improved long-term potentiation and cognitive functions in Alzheimer's disease mice. Several lines of evidence have suggested that Nogo-A and the Nogo-66 receptor 1 (NgR1), which form a complex that inhibits long-term potentiation and cognitive function, might be associated with the adiponectin receptor 1 (AdipoR1), which is a receptor for osmotin...
January 15, 2018: Molecular Neurobiology
Donghua Wu, Baofeng Zhao, Xiaoyu Qi, Fang Peng, Hailu Fu, Xinming Chi, Qing Robert Miao, Shujuan Shao
Nogo-B receptor (NgBR) is a specific receptor of Nogo-B that regulates vascular remodeling and angiogenesis. Previously, we found that NgBR promotes the membrane translocation and activation of Ras in breast cancer cells and enhances the chemoresistance of hepatocellular carcinoma cells to 5-fluorouracil. However, the role of NgBR in lung cancer has not yet been elucidated. In the present study, we found that NgBR knockdown inhibited epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells in vitro and metastasis of NSCLC cells in vivo...
January 10, 2018: Cancer Letters
Jiang-Yi He, Ping Han, Yu Zhang, Yong-Dong Liu, Shi-Jian Song, Guo-Kai Feng, Yu An, Ai-Jun Zhou, Hong-Bo Wang, Li Yuan, Zhi-Rui Lin, Tian-Liang Xia, Man-Zhi Li, Yan-Min Liu, Xiao-Ming Huang, Hua Zhang, Qian Zhong
Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines...
January 11, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Robert G Farrer, Gwendolyn L Kartje
The Nogo-A protein, originally discovered as a potent myelin-associated inhibitor of neurite outgrowth, is also expressed by certain neurons, especially during development and after injury, but its role in neuronal function is not completely known. In this report, we overexpressed Nogo-A in PC12 cells to use as a model to identify potential neuronal signaling pathways affected by endogenously expressed Nogo-A. Unexpectedly, our results show that viability of Nogo-A-overexpressing cells was reduced progressively due to apoptotic cell death following NGF treatment, but only after 24 h...
January 8, 2018: Cellular Signalling
Adam R Griffith, Claude J Rogers, Gregory M Miller, Ravinder Abrol, Linda C Hsieh-Wilson, William A Goddard
Cell-surface carbohydrates play important roles in numerous biological processes through their interactions with various protein-binding partners. These interactions are made possible by the vast structural diversity of carbohydrates and the diverse array of carbohydrate presentations on the cell surface. Among the most complex and important carbohydrates are glycosaminoglycans (GAGs), which display varied stereochemistry, chain lengths, and patterns of sulfation. GAG-protein interactions participate in neuronal development, angiogenesis, spinal cord injury, viral invasion, and immune response...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
Wenwen Zhang, Xiaoxiao Yang, Yuanli Chen, Wenquan Hu, Lipei Liu, Xiaomeng Zhang, Mengyang Liu, Lei Sun, Ying Liu, Miao Yu, Xiaoju Li, Luyuan Li, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum...
February 2018: Biochimica et Biophysica Acta
Ricardo L Sanz, Gino B Ferraro, Johannes Kacervosky, Charleen Salesse, Elizabeth Gowing, Luyang Hua, Isabel Rambaldi, Francois Beaubien, Kenn Holmbeck, J F Cloutier, Martin Lévesque, Keith Murai, Alyson E Fournier
Cell-surface molecules are dynamically regulated at the synapse to assemble and disassemble adhesive contacts that are important for synaptogenesis and for tuning synaptic transmission. Metalloproteinases dynamically regulate cellular behaviors through the processing of cell surface molecules. In the present study, we evaluated the role of membrane-type metalloproteinases (MT-MMPs) in excitatory synaptogenesis. We find that MT3-MMP and MT5-MMP are broadly expressed in the mouse cerebral cortex and that MT3-MMP loss-of-function interferes with excitatory synapse development in dissociated cortical neurons and in vivo We identify Nogo-66 receptor (NgR1) as an MT3-MMP substrate that is required for MT3-MMP-dependent synapse formation...
January 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yuehui Zhou, Cuicui Li, Rena Li, Chenglin Zhou
The adolescent brain is vulnerable to long-lasting cognitive disturbances resulting from nicotine exposure. Although exercise has been used as an intervention for ameliorating cognitive deficits in various disorders, the effect on cognitive changes induced by nicotine exposure and its underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of exercise on nicotine reward-associated cognitive behaviors in adolescent rats subjected to nicotine conditioned place preference paradigm (CPP)...
November 29, 2017: Journal of Cellular Physiology
Yong-Yan Bi, Yong Quan
Accumulating data strongly suggests that leukocyte immunoglobulin like receptor B1 (PirB) inhibits axonal outgrowth. However, the underlying mechanisms remain unclear. In the present study, cortical neurons of newborn mice were cultured with Nogo‑66 (Nogo‑p4; 4 µmol/l; a PirB ligand) together with NEP1‑40 (Nogo inhibitory peptide) and/or anti‑PirB body (50 mg/ml). PirB mRNA and protein was higher in cultured neurons induced by Nogo‑66 compared with untreated cells. Neurite outgrowth assays demonstrated that the inhibitory effects of Nogo‑66 on axonal outgrowth were reversed by anti‑PirB body...
January 2018: Molecular Medicine Reports
Matti F Pronker, Roderick P Tas, Hedwich C Vlieg, Bert J C Janssen
The Nogo Receptor (NgR) is a glycophosphatidylinositol-anchored cell-surface protein and is a receptor for three myelin-associated inhibitors of regeneration: myelin-associated glycoprotein, Nogo66 and oligodendrocyte myelin glycoprotein. In combination with different co-receptors, NgR mediates signalling that reduces neuronal plasticity. The available structures of the NgR ligand-binding leucine-rich repeat (LRR) domain have an artificial disulfide pattern owing to truncated C-terminal construct boundaries...
November 1, 2017: Acta Crystallographica. Section D, Structural Biology
Lihong Nan, Lan Yang, Yanfang Zheng, Yibo He, Qingqing Xie, Zheming Chen, Huang Li, Mei Huang
Gualou Guizhi decoction (GLGZD) is effective for the clinical treatment of limb spasms caused by ischemic stroke, but its underlying mechanism is unclear. Propidium iodide (PI) fluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemistry, western blot, and real-time qPCR were used to observe the axonal regeneration and neuroprotective effects of GLGZD aqueous extract on organotypic cortical slices exposed to oxygen-glucose deprivation (OGD) and further elucidate the potential mechanisms...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Shuang-Lian Long, Yu-Kun Li, Yuan-Jie Xie, Zhi-Feng Long, Jin-Feng Shi, Zhong-Cheng Mo
Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis...
December 2017: DNA and Cell Biology
Kun Zeng, Bo Zhong, Xiao-Li Shen, Min Fang, Bao-Tao Lin, Da-Hui Ma
We investigated the effects of lentivirus-mediated RNAi targeting of Nogo Receptor (NgR) on the proliferation and survival of murine retinal ganglion cells (mRGCs) in vitro and in vivo. Cultured mRGCs and C57BL/6 male mice were divided into 4 experimental groups: blank, model [100 μM N-methyl-D-aspartate (NMDA)], nscRNA (100 μM NMDA+ nscRNA vectors) and siNgR (100 μM NMDA+ siNgR vectors). CCK-8 and flow cytometry analyses revealed that silencing NgR enhanced proliferation, cell cycling and survival of NMDA-treated mRGCs...
September 12, 2017: Oncotarget
S Azar, N Leventoux, C Ripoll, V Rigau, C Gozé, F Lorcy, L Bauchet, H Duffau, P O Guichet, B Rothhut, J P Hugnot
Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain tumors that often progress into high grade gliomas. Most tumors have a missense mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their environment and the pathways activated in these tumors are still ill-defined and are mainly based on genomics and transcriptomics analysis. Here we used freshly-resected tumors to accurately characterize the tumoral cell population and their environment...
October 13, 2017: Glia
Yanjun Zhao, Sivaprakash Sivaji, Michael C Chiang, Haadi Ali, Monica Zukowski, Sareen Ali, Bryan Kennedy, Alex Sklyar, Alice Cheng, Zihan Guo, Alexander K Reed, Ravindra Kodali, Jennifer Borowski, Georgia Frost, Patrick Beukema, Zachary P Wills
Compelling evidence links amyloid beta (Aβ) peptide accumulation in the brains of Alzheimer's disease (AD) patients with the emergence of learning and memory deficits, yet a clear understanding of the events that drive this synaptic pathology are lacking. We present evidence that neurons exposed to Aβ are unable to form new synapses, resulting in learning deficits in vivo. We demonstrate the Nogo receptor family (NgR1-3) acts as Aβ receptors mediating an inhibition of synapse assembly, plasticity, and learning...
October 11, 2017: Neuron
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