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https://www.readbyqxmd.com/read/28526701/netrin-1-preserves-blood-brain-barrier-integrity-through-deleted-in-colorectal-cancer-focal-adhesion-kinase-rhoa-signaling-pathway-following-subarachnoid-hemorrhage-in-rats
#1
Zongyi Xie, Budbazar Enkhjargal, Cesar Reis, Lei Huang, Weifeng Wan, Jiping Tang, Yuan Cheng, John H Zhang
BACKGROUND: Netrin-1 (NTN-1) has been established to be a novel intrinsic regulator of blood-brain barrier (BBB) maintenance. This study was carried out to investigate the potential roles of exogenous NTN-1 in preserving BBB integrity after experimental subarachnoid hemorrhage (SAH) as well as the underlying mechanisms of its protective effects. METHODS AND RESULTS: A total of 309 male Sprague-Dawley rats were subjected to an endovascular perforation model of SAH...
May 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28521119/netrin-mediated-axon-guidance-to-the-cns-midline-revisited
#2
Randal A Hand, Alex L Kolodkin
Varadarajan et al. (2017)-in this issue of Neuron-and Dominici et al. (2017)-published online at Nature-independently show that floor plate-derived netrin-1 is dispensable for commissural neuron axon guidance to the CNS midline during development.
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28501620/molecular-characterization-of-netrin-1-and-app-receptor-binding-new-leads-to-block-the-progression-of-senile-plaques-in-alzheimer-s-disease
#3
Franck Borel, Fanny Marzocca, Jean-Guy Delcros, Nicolas Rama, Patrick Mehlen, Jean-Luc Ferrer
Alzheimer's disease is a growing concern in the context of the increasing lifespan of the populations. The work presented here is part of the fight against this threat. It supports a therapeutic approach to reduce the incidence of Alzheimer's disease, taking advantage of the specific binding of several domains of Netrin-1 to the β-amyloid precursor protein. This basic knowledge shall then be used to predict, design or characterize lead compounds that may in turn inhibit/delay Alzheimer's disease progression, extending the therapeutic offer of the other leads already being investigated in this line...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28489749/association-between-pax7-and-ntn1-gene-polymorphisms-and-nonsyndromic-orofacial-clefts-in-a-northern-chinese-population
#4
Qiang Guo, Dongmei Li, Xiangbiao Meng, Tingting Liu, Jinna Shi, Yanru Hao, Xiaohui Jiao, Kewen Lv, Tenglong Hu, Tao Song
BACKGROUND: Nonsyndromic orofacial clefts (NSOC) are the most common orofacial congenital defect with a complex etiology. Genome-wide association studies have identified paired box protein 7 (PAX7) and netrin-1 (NTN1) as candidate susceptibility genes for NSOC in both European and Asian populations. Here, possible associations between single-nucleotide polymorphisms (SNPs) in or near PAX7 and NTN1 were investigated in relation to risk of NSOC in a northern Chinese population. METHODS: A total of 602 individuals with NSOC and 510 controls were recruited from northern China...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28489275/recent-drug-therapies-for-corneal-neovascularization
#5
REVIEW
Xinyao Liu, Shurong Wang, Xuanzhong Wang, Jiaming Liang, Yan Zhang
Corneal neovascularization (CNV) is a common pathological change in ocular surface diseases. It is not only the factor that affects vision, but also the main cause for corneal graft failure. Based on the mechanism of CNV, many achievements have been developed to suppress the formation of CNV. There are certain novel drugs such as aflibercept, gold nanoparticles and netrins which provide us with new clues to treat CNV. However, we still need to develop more effective therapeutic drugs. It is of great significance to develop new effective drugs to suppress the occurrence of CNV...
May 10, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28483977/uncoupling-of-unc5c-with-polymerized-tubb3-in-microtubules-mediates-netrin-1-repulsion
#6
Qiangqiang Shao, Tao Yang, Huai Huang, Farrah Alarmanazi, Guofa Liu
Modulation of microtubule (MT) dynamics is a key event of cytoskeleton remodeling in the growth cone (GC) during axon outgrowth and pathfinding. Our previous studies have shown that the direct interaction of netrin receptor DCC and DSCAM with polymerized TUBB3, a neuron-specific MT subunit in the brain, is required for netrin-1-mediated axon outgrowth, branching and attraction. Here, we show that uncoupling of polymerized TUBB3 with netrin-1 repulsive receptor UNC5C is involved in netrin-1-mediated axonal repulsion...
May 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28475012/the-role-of-sox6-and-netrin-1-in-ovarian-cancer-cell-growth-invasiveness-and-angiogenesis
#7
Yi Li, Ming Xiao, Fangchun Guo
SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28445456/floor-plate-derived-netrin-1-is-dispensable-for-commissural-axon-guidance
#8
Chloé Dominici, Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Quentin Rappeneau, Nicolas Rama, Pauline Vieugue, Agns Bernet, Patrick Mehlen, Alain Chédotal
Netrin-1 is an evolutionarily conserved, secreted extracellular matrix protein involved in axon guidance at the central nervous system midline. Netrin-1 is expressed by cells localized at the central nervous system midline, such as those of the floor plate in vertebrate embryos. Growth cone turning assays and three-dimensional gel diffusion assays have shown that netrin-1 can attract commissural axons. Loss-of-function experiments further demonstrated that commissural axon extension to the midline is severely impaired in the absence of netrin-1 (refs 3, 7, 8, 9)...
May 18, 2017: Nature
https://www.readbyqxmd.com/read/28443497/netrin-1-in-cancer-potential-biomarker-and-therapeutic-target
#9
Umut Kefeli, Aysegul Ucuncu Kefeli, Devrim Cabuk, Ulas Isik, Alper Sonkaya, Ozgur Acikgoz, Ercan Ozden, Kazim Uygun
Netrin-1, a laminin-related protein, is known to be involved in the nervous system development. Recently, Netrin-1's involvement in other processes such as cell adhesion, motility, proliferation, and differentiation that are important for the development of epithelial tissues has been described. In addition, Netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated-5 homolog, have been linked to apoptosis and angiogenesis. Since these properties are essential for tumor development, Netrin-1 and its receptors have been reported to promote tumorigenesis in many types of cancers...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28438858/functional-roles-of-netrin-1-in-osteoblast-differentiation
#10
Tsuyoshi Sato, Shoichiro Kokabu, Yuichiro Enoki, Naoki Hayashi, Masahito Matsumoto, Mitsuhiko Nakahira, Masashi Sugasawa, Tetsuya Yoda
AIM: Recent studies have demonstrated that netrin-1 plays a vital role in bone metabolism. Previous studies have shown that osteoblasts produce netrin-1 which affects osteoclast differentiation. However, the role of netrin-1 in osteoblast differentiation is not well understood. In this study, we explored the roles of netrin-1 in osteoblasts. MATERIALS AND METHODS: Quantitative reverse-transcriptase polymerase chain reaction (qPCR), RNA interference for netrin receptors, the generation of netrin-1 plasmid, transfection of plasmids, and cell proliferation assay were performed...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28434801/netrin1-produced-by-neural-progenitors-not-floor-plate-cells-is-required-for-axon-guidance-in-the-spinal-cord
#11
Supraja G Varadarajan, Jennifer H Kong, Keith D Phan, Tzu-Jen Kao, S Carmen Panaitof, Julie Cardin, Holger Eltzschig, Artur Kania, Bennett G Novitch, Samantha J Butler
Netrin1 has been proposed to act from the floor plate (FP) as a long-range diffusible chemoattractant for commissural axons in the embryonic spinal cord. However, netrin1 mRNA and protein are also present in neural progenitors within the ventricular zone (VZ), raising the question of which source of netrin1 promotes ventrally directed axon growth. Here, we use genetic approaches in mice to selectively remove netrin from different regions of the spinal cord. Our analyses show that the FP is not the source of netrin1 directing axons to the ventral midline, while local VZ-supplied netrin1 is required for this step...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28389207/netrin-1-improves-the-amyloid-%C3%AE-mediated-suppression-of-memory-and-synaptic-plasticity
#12
Mohammad Shabani, Masoud Haghani, Parisa Esmaeili Tazangi, Mahnaz Bayat, Seyed Mostafa Shid Moosavi, Hoda Ranjbar
The aim of this study was to investigate the effects of netrin-1 (NT-1) on amyloid-beta (Aβ)-induced impairments in learning-memory and synaptic plasticity. The NT-1 or its vehicle was administered four times into the Aβ+NT or Aβ+V groups, respectively. The Aβ+SNT group received a single dose of NT-1. The Aβ+HNT group received heat-inactivated NT-1. For the learning-memory and synaptic plasticity assessment, field potentials recording and behavioral experiment were used. Bilateral injection of Aβ1-42 inhibits induction of long-term potentiation (LTP) and decreased memory performance in all the behavioral tasks...
April 4, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28386060/single-molecule-translation-imaging-visualizes-the-dynamics-of-local-%C3%AE-actin-synthesis-in-retinal-axons
#13
Florian Ströhl, Julie Qiaojin Lin, Romain F Laine, Hovy Ho-Wai Wong, Vasja Urbančič, Roberta Cagnetta, Christine E Holt, Clemens F Kaminski
Local mRNA translation occurs in growing axons enabling precise control of the proteome in response to signals. To measure quantitatively the spatiotemporal dynamics of protein synthesis in growth cones, we further developed a technique for single molecule translation imaging (SMTI). We report that Netrin-1 triggers a burst of β-actin synthesis at multiple non-repetitive sites, particularly in the periphery. The response is remarkably rapid starting within 20 seconds of cue application.
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28384160/a-wnt-planar-polarity-pathway-instructs-neurite-branching-by-restricting-f-actin-assembly-through-endosomal-signaling
#14
Chun-Hao Chen, Chun-Wei He, Chien-Po Liao, Chun-Liang Pan
Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues. Here we show that in C. elegans, the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons. Wnts function through MIG-1/Frizzled and the planar cell polarity protein (PCP) VANG-1/Strabismus/Vangl2 to restrict the formation of F-actin patches, which mark branching sites in nascent neurites. We find that VANG-1 promotes Wnt signaling by facilitating Frizzled endocytosis and genetically acts in a common pathway with arr-1/β-arrestin, whose mutation results in defective PLM branching and F-actin patterns similar to those in the Wnt, mig-1 or vang-1 mutants...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28373074/netrin-1-mediates-protective-effects-exerted-by-insulin-like-growth-factor-1-on-cochlear-hair-cells
#15
Kohei Yamahara, Takayuki Nakagawa, Juichi Ito, Kazuo Kinoshita, Koichi Omori, Norio Yamamoto
Sensorineural hearing loss (SNHL) is mainly caused by the damage of cochlear hair cells (HCs). As HCs and supporting cells (SCs) do not proliferate in postnatal mammals, the loss of HCs and SCs is irreversible, emphasizing the importance of preserving their numbers to prevent SNHL. It is known that insulin-like growth factor 1 (IGF1) is instrumental in the treatment of SNHL. Our previous study indicates that IGF1 protects HCs against aminoglycoside by activating IGF1 receptor and its two major downstream pathways, PI3K/AKT and MEK/ERK, in SCs, which results in the upregulation of the expression of the Netrin1-encoding gene (Ntn1)...
April 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28347836/intranasal-administration-of-recombinant-netrin-1-attenuates-neuronal-apoptosis-by-activating-dcc-appl-1-akt-signaling-pathway-after-subarachnoid-hemorrhage-in-rats
#16
Zongyi Xie, Lei Huang, Budbazar Enkhjargal, Cesar Reis, Weifeng Wan, Jiping Tang, Yuan Cheng, John H Zhang
Neuronal apoptosis is a crucial pathological process in early brain injury after subarachnoid hemorrhage (SAH). The effective therapeutic strategies to ameliorate neuronal apoptosis are still absent. We intended to determine whether intranasal administration of exogenous Netrin-1 (NTN-1) could attenuate neuronal apoptosis after experimental SAH, specifically via activating DCC-dependent APPL-1/AKT signaling cascade. Two hundred twenty-five male Sprague-Dawley rats were subjected to the endovascular perforation model of SAH...
March 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28341853/non-cell-autonomous-role-of-dcc-in-the-guidance-of-the-corticospinal-tract-at-the-midline
#17
Quentin Welniarz, Marie-Pierre Morel, Oriane Pourchet, Cécile Gallea, Jean-Charles Lamy, Massimo Cincotta, Mohamed Doulazmi, Morgane Belle, Aurélie Méneret, Oriane Trouillard, Marta Ruiz, Vanessa Brochard, Sabine Meunier, Alain Trembleau, Marie Vidailhet, Alain Chédotal, Isabelle Dusart, Emmanuel Roze
DCC, a NETRIN-1 receptor, is considered as a cell-autonomous regulator for midline guidance of many commissural populations in the central nervous system. The corticospinal tract (CST), the principal motor pathway for voluntary movements, crosses the anatomic midline at the pyramidal decussation. CST fails to cross the midline in Kanga mice expressing a truncated DCC protein. Humans with heterozygous DCC mutations have congenital mirror movements (CMM). As CMM has been associated, in some cases, with malformations of the pyramidal decussation, DCC might also be involved in this process in human...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274689/combined-wharton-s-jelly-derived-mesenchymal-stem-cells-and-nerve-guidance-conduit-a-potential-promising-therapy-for-peripheral-nerve-injuries
#18
Sally M Shalaby, Amal S El-Shal, Faiza E Ahmed, Sahar F Shaban, Rania A Wahdan, Wael A Kandel, Mohammed S Senger
BACKGROUND: Peripheral nerve injuries represent a clinical problem with insufficient or unsatisfactory treatment options. Functional outcome with nerve guidance conduits was unsatisfactory in nerve defects with increased gap size. So, cell therapy may benefit as a tool for optimizing the regeneration process. The aim of the present study was to evaluate the impact of combination of cell therapy and nerve guidance conduits on the nerve regeneration and on the expression of the factors aiding the regeneration in a rat model of sciatic nerve injury...
March 6, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28253401/netrin-4-mediates-corneal-hemangiogenesis-but-not-lymphangiogenesis-in-the-mouse-model-of-suture-induced-neovascularization
#19
Anna-Karina B Maier, Sabrina Klein, Norbert Kociok, Aline I Riechardt, Enken Gundlach, Nadine Reichhart, Olaf Strauß, Antonia M Joussen
Purpose: Netrin-4, a secreted protein, is found in the basement membrane of blood vessels and acts as a key regulator of angiogenesis. Here we investigated the role of Netrin-4 in the mouse-model of suture-induced corneal hem- and lymphangiogenesis. Methods: Corneal hem- and lymphangiogenesis were induced in Netrin-4-deficient (Ntn4-/-) and wild-type (WT) mice by placing three 11-0 nylon sutures intrastromally. Fourteen days after suturing, the vascularized area was analyzed via corneal flat mount immunohistochemistry...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28251919/netrin-1-receptor-antibodies-in-thymoma-associated-neuromyotonia-with-myasthenia-gravis
#20
Estefanía Torres-Vega, Nuria Mancheño, Arantxa Cebrián-Silla, Vicente Herranz-Pérez, María J Chumillas, Germán Moris, Bastien Joubert, Jérôme Honnorat, Teresa Sevilla, Juan J Vílchez, Josep Dalmau, Francesc Graus, José Manuel García-Verdugo, Luis Bataller
OBJECTIVE: To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications. METHODS: Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers)...
March 28, 2017: Neurology
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