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acetylcholine wnt

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https://www.readbyqxmd.com/read/27328992/r-spondin-2-promotes-acetylcholine-receptor-clustering-at-the-neuromuscular-junction-via-lgr5
#1
Hiroaki Nakashima, Bisei Ohkawara, Shinsuke Ishigaki, Takayasu Fukudome, Kenyu Ito, Mikito Tsushima, Hiroyuki Konishi, Tatsuya Okuno, Toshiro Yoshimura, Mikako Ito, Akio Masuda, Gen Sobue, Hiroshi Kiyama, Naoki Ishiguro, Kinji Ohno
At the neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is mediated by spinal motor neuron (SMN)-derived agrin and its receptors on the muscle, the low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific receptor tyrosine kinase (MuSK). Additionally, AChR clustering is mediated by the components of the Wnt pathway. Laser capture microdissection of SMNs revealed that a secreted activator of Wnt signaling, R-spondin 2 (Rspo2), is highly expressed in SMNs. We found that Rspo2 is enriched at the NMJ, and that Rspo2 induces MuSK phosphorylation and AChR clustering...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27151977/diverging-roles-for-lrp4-and-wnt-signaling-in-neuromuscular-synapse-development-during-evolution
#2
Leonor Remédio, Katherine D Gribble, Jennifer K Lee, Natalie Kim, Peter T Hallock, Nicolas Delestrée, George Z Mentis, Robert C Froemke, Michael Granato, Steven J Burden
Motor axons approach muscles that are prepatterned in the prospective synaptic region. In mice, prepatterning of acetylcholine receptors requires Lrp4, a LDLR family member, and MuSK, a receptor tyrosine kinase. Lrp4 can bind and stimulate MuSK, strongly suggesting that association between Lrp4 and MuSK, independent of additional ligands, initiates prepatterning in mice. In zebrafish, Wnts, which bind the Frizzled (Fz)-like domain in MuSK, are required for prepatterning, suggesting that Wnts may contribute to prepatterning and neuromuscular development in mammals...
May 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27119269/roles-of-collagen-q-in-musk-antibody-positive-myasthenia-gravis
#3
Kinji Ohno, Kenji Otsuka, Mikako Ito
The low-density lipoprotein receptor-related protein 4 (LRP4) and the muscle-specific receptor tyrosine kinase (MuSK) form a tetrameric protein complex on the postsynaptic membrane at the neuromuscular junction (NMJ). Binding of agrin to LRP4 triggers phosphorylation of MuSK. Activated MuSK drives clustering of acetylcholine receptor (AChR). Wnt ligands also directly bind to MuSK to induce AChR clustering. MuSK anchors the acetylcholinesterase (AChE)/collagen Q (ColQ) complex to the synaptic basal lamina. In addition, an extracellular proteoglycan, biglycan, binds to MuSK...
November 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/26818866/nicotinic-acetylcholine-receptors-in-the-pathophysiology-of-al-zheimer-s-disease-the-role-of-protein-protein-interactions-in-current-and-future-treatment
#4
Morten Skøtt Thomsen, Jesper Tobias Andreasen, Maria Arvaniti, Kristi Anne Kohlmeier
Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus, and their demonstrated role in processes underlying cognition such as synaptic facilitation, and theta and gamma wave activity. Historically, activity at these receptors is facilitated in AD by use of drugs that increase the levels of their endogenous agonist acetylcholine, and more recently nAChR selective ligands have undergone clinical trials...
2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/26074265/the-%C3%AE-7-nicotinic-acetylcholine-receptor-a-mediator-of-pathogenesis-and-therapeutic-target-in-autism-spectrum-disorders-and-down-syndrome
#5
REVIEW
Stephen I Deutsch, Jessica A Burket, Maria R Urbano, Andrew D Benson
Currently, there are no medications that target core deficits of social communication and restrictive, repetitive patterns of behavior in persons with autism spectrum disorders (ASDs). Adults with Down syndrome (DS) display a progressive worsening of adaptive functioning, which is associated with Alzheimer's disease (AD)-like histopathological changes in brain. Similar to persons with ASDs, there are no effective medication strategies to prevent or retard the progressive worsening of adaptive functions in adults with DS...
October 15, 2015: Biochemical Pharmacology
https://www.readbyqxmd.com/read/26001208/nicotine-contributes-to-the-neural-stem-cells-fate-against-toxicity-of-microglial-derived-factors-induced-by-a%C3%AE-via-the-wnt-%C3%AE-catenin-pathway
#6
De-Qi Jiang, Mei-Dan Wei, Ke-Wan Wang, Yan-Xian Lan, Ning Zhu, Yong Wang
Recent studies have demonstrated that the molecules secreted from microglias play important roles in the cell fate determination of neural stem cells (NSCs), and nicotinic acetylcholine receptor agonist treatment could reduce neuroinflammation in some neurodegenerative disease models, such as Alzheimer's disease (AD). However, it is not clear how nicotine plays a neuroprotective role in inflammation-mediated central nervous diseases, and its possible mechanisms in the process remain largely elusive. The aim of this study is to improve the survival microenvironment of NSCs co-cultured with microglias in vitro by weakening inflammation that mediated by accumulation of β-amyloid peptide (Aβ)...
2016: International Journal of Neuroscience
https://www.readbyqxmd.com/read/25743255/activation-of-the-wnt-%C3%AE-catenin-signaling-cascade-after-traumatic-nerve-injury
#7
S Kurimoto, J Jung, M Tapadia, J Lengfeld, D Agalliu, M Waterman, T Mozaffar, R Gupta
Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via β-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and β-catenin are associated with NMJ destabilization following traumatic denervation...
May 21, 2015: Neuroscience
https://www.readbyqxmd.com/read/25354590/hnrnp-c-yb-1-and-hnrnp-l-coordinately-enhance-skipping-of-human-musk-exon-10-to-generate-a-wnt-insensitive-musk-isoform
#8
Farhana Nasrin, Mohammad Alinoor Rahman, Akio Masuda, Kenji Ohe, Jun-Ichi Takeda, Kinji Ohno
Muscle specific receptor tyrosine kinase (MuSK) is an essential postsynaptic transmembrane molecule that mediates clustering of acetylcholine receptors (AChR). MUSK exon 10 is alternatively skipped in human, but not in mouse. Skipping of this exon disrupts a cysteine-rich region (Fz-CRD), which is essential for Wnt-mediated AChR clustering. To investigate the underlying mechanisms of alternative splicing, we exploited block-scanning mutagenesis with human minigene and identified a 20-nucleotide block that contained exonic splicing silencers...
2014: Scientific Reports
https://www.readbyqxmd.com/read/25143365/denervation-suppresses-gastric-tumorigenesis
#9
Chun-Mei Zhao, Yoku Hayakawa, Yosuke Kodama, Sureshkumar Muthupalani, Christoph B Westphalen, Gøran T Andersen, Arnar Flatberg, Helene Johannessen, Richard A Friedman, Bernhard W Renz, Arne K Sandvik, Vidar Beisvag, Hiroyuki Tomita, Akira Hara, Michael Quante, Zhishan Li, Michael D Gershon, Kazuhiro Kaneko, James G Fox, Timothy C Wang, Duan Chen
The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach...
August 20, 2014: Science Translational Medicine
https://www.readbyqxmd.com/read/24860427/frizzled-9-impairs-acetylcholine-receptor-clustering-in-skeletal-muscle-cells
#10
Evelyn C Avilés, Cristina Pinto, Patricia Hanna, Jorge Ojeda, Viviana Pérez, Giancarlo V De Ferrari, Pedro Zamorano, Miguel Albistur, Daniel Sandoval, Juan P Henríquez
Cumulative evidence indicates that Wnt pathways play crucial and diverse roles to assemble the neuromuscular junction (NMJ), a peripheral synapse characterized by the clustering of acetylcholine receptors (AChR) on postsynaptic densities. The molecular determinants of Wnt effects at the NMJ are still to be fully elucidated. We report here that the Wnt receptor Frizzled-9 (Fzd9) is expressed in developing skeletal muscles during NMJ synaptogenesis. In cultured myotubes, gain- and loss-of-function experiments revealed that Fzd9-mediated signaling impairs the AChR-clustering activity of agrin, an organizer of postsynaptic differentiation...
2014: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/24631402/caspase-3-cleavage-of-dishevelled-induces-elimination-of-postsynaptic-structures
#11
Jin-Yuan Wang, Fei Chen, Xiu-Qing Fu, Chuang-Shi Ding, Li Zhou, Xiao-Hui Zhang, Zhen-Ge Luo
During the development of vertebrate neuromuscular junction (NMJ), agrin stabilizes, whereas acetylcholine (ACh) destabilizes AChR clusters, leading to the refinement of synaptic connections. The intracellular mechanism underlying this counteractive interaction remains elusive. Here, we show that caspase-3, the effector protease involved in apoptosis, mediates elimination of AChR clusters. We found that caspase-3 was activated by cholinergic stimulation of cultured muscle cells without inducing cell apoptosis and that this activation was prevented by agrin...
March 31, 2014: Developmental Cell
https://www.readbyqxmd.com/read/24376645/nicotine-deteriorates-the-osteogenic-differentiation-of-periodontal-ligament-stem-cells-through-%C3%AE-7-nicotinic-acetylcholine-receptor-regulating-wnt-pathway
#12
Zhifei Zhou, Bei Li, Zhiwei Dong, Fen Liu, Yu Zhang, Yang Yu, Fengqing Shang, Lizheng Wu, Xiaojing Wang, Yan Jin
AIMS: Cigarette smoking is one of the high risk factors of adult chronic periodontitis and nicotine is the well established toxic substance in cigarette. However, the mechanism of nicotine induced periodontitis is still unknown. Here we studied whether nicotine impaired the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) through activating α7 nicotinic acetylcholine receptor (α7 nAChR). METHODS: hPDLSCs with multi differentiation potential and surface makers for mesenchymal stem cells were harvested by limiting dilution technique...
2013: PloS One
https://www.readbyqxmd.com/read/24014138/wnt-signaling-in-skeletal-muscle-dynamics-myogenesis-neuromuscular-synapse-and-fibrosis
#13
REVIEW
Pedro Cisternas, Juan P Henriquez, Enrique Brandan, Nibaldo C Inestrosa
The signaling pathways activated by Wnt ligands are related to a wide range of critical cell functions, such as cell division, migration, and synaptogenesis. Here, we summarize compelling evidence on the role of Wnt signaling on several features of skeletal muscle physiology. We briefly review the role of Wnt pathways on the formation of muscle fibers during prenatal and postnatal myogenesis, highlighting its role on the activation of stem cells of the adult muscles. We also discuss how Wnt signaling regulates the precise formation of neuromuscular synapses, by modulating the differentiation of presynaptic and postsynaptic components, particularly regarding the clustering of acetylcholine receptors on the muscle membrane...
February 2014: Molecular Neurobiology
https://www.readbyqxmd.com/read/23914941/electrical-stimulation-modulates-wnt-signaling-and-regulates-genes-for-the-motor-endplate-and-calcium-binding-in-muscle-of-rats-with-spinal-cord-transection
#14
Yong Wu, Lauren Collier, Weiping Qin, Graham Creasey, William A Bauman, Jonathan Jarvis, Christopher Cardozo
BACKGROUND: Spinal cord injury (SCI) results in muscle atrophy and a shift of slow oxidative to fast glycolytic fibers. Electrical stimulation (ES) at least partially restores muscle mass and fiber type distribution. The objective of this study was to was to characterize the early molecular adaptations that occur in rat soleus muscle after initiating isometric resistance exercise by ES for one hour per day for 1, 3 or 7 days when ES was begun 16 weeks after SCI. Additionally, changes in mRNA levels after ES were compared with those induced in soleus at the same time points after gastrocnemius tenotomy (GA)...
August 2, 2013: BMC Neuroscience
https://www.readbyqxmd.com/read/23874651/rna-deep-sequencing-analysis-reveals-that-nicotine-restores-impaired-gene-expression-by-viral-proteins-in-the-brains-of-hiv-1-transgenic-rats
#15
Junran Cao, Shaolin Wang, Ju Wang, Wenyan Cui, Tanseli Nesil, Michael Vigorito, Sulie L Chang, Ming D Li
Persons infected with HIV-1 often develop neurologic disorders despite receiving highly active anti-retroviral therapy. Although the underlying mechanism is largely undetermined, our previous RNA-seq-based study showed that the expression of many genes was altered in the central nervous system (CNS) of HIV-1 transgenic (HIV-1Tg) rats. Because nicotine, a natural agonist of nicotinic acetylcholine receptors, exhibits a neuroprotective effect, we presently tested the hypothesis that nicotine restores the expression of altered genes in the CNS of HIV-1Tg rats...
2013: PloS One
https://www.readbyqxmd.com/read/23850867/maldevelopment-of-dermal-lymphatics-in-wnt5a-knockout-mice
#16
Kerstin Buttler, Jürgen Becker, Tobias Pukrop, Jörg Wilting
Maintenance of tissue homeostasis and immune surveillance are important functions of the lymphatic vascular system. Lymphatic vessels are lined by lymphatic endothelial cells (LECs). By gene micro-array expression studies we recently compared human lymphangioma-derived LECs with umbilical vein endothelial cells (HUVECs). Here, we followed up on these studies. Besides well-known LEC markers, we observed regulation of molecules involved in immune regulation, acetylcholine degradation and platelet regulation. Moreover we identified differentially expressed WNT pathway components, which play important roles in the morphogenesis of various organs, including the blood vascular system...
September 15, 2013: Developmental Biology
https://www.readbyqxmd.com/read/23842742/nicotine-prevents-synaptic-impairment-induced-by-amyloid-%C3%AE-oligomers-through-%C3%AE-7-nicotinic-acetylcholine-receptor-activation
#17
Nibaldo C Inestrosa, Juan A Godoy, Jessica Y Vargas, Macarena S Arrazola, Juvenal A Rios, Francisco J Carvajal, Felipe G Serrano, Ginny G Farias
An emerging view on Alzheimer disease's (AD) pathogenesis considers amyloid-β (Aβ) oligomers as a key factor in synaptic impairment and rodent spatial memory decline. Alterations in the α7-nicotinic acetylcholine receptor (α7-nAChR) have been implicated in AD pathology. Herein, we report that nicotine, an unselective α7-nAChR agonist, protects from morphological and synaptic impairments induced by Aβ oligomers. Interestingly, nicotine prevents both early postsynaptic impairment and late presynaptic damage induced by Aβ oligomers through the α7-nAChR/phosphatidylinositol-3-kinase (PI3K) signaling pathway...
September 2013: Neuromolecular Medicine
https://www.readbyqxmd.com/read/23252893/structure-of-the-neuromuscular-junction-function-and-cooperative-mechanisms-in-the-synapse
#18
REVIEW
Masaharu Takamori
As an overview of the structure of the neuromuscular junction, three items are described focusing on cooperative mechanisms involving the synapse and leading to muscle contraction: (1) presynaptic acetylcholine release regulated by vesicle cycling (exocytosis and endocytosis); the fast-mode of endocytosis requires a large influx of external Ca(2+) and is promoted by the activation of G protein-coupled receptors and receptor tyrosine kinases; (2) postsynaptic acetylcholine receptor clustering mediated by the muscle-specific, Dok7-stimulated tyrosine kinase (MuSK) through two signaling mechanisms: one via agrin-Lrp4-MuSK (Ig1/2 domains) and the second via Wnt-MuSK (Frizzled-like cysteine-rich domain)-adaptor Dishevelled; Wnts/MuSK and Lrp4 direct a retrograde signal to presynaptic differentiation; (3) muscle contractile machinery regulated by Ca(2+) -release and Ca(2+) -influx channels, including the depolarization-activated ryanodine receptor-1 and the receptor- and/or store-operated transient receptor potential canonical...
December 2012: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/22999188/antibodies-against-wnt-receptor-of-muscle-specific-tyrosine-kinase-in-myasthenia-gravis
#19
Masaharu Takamori, Tatsufumi Nakamura, Masakatsu Motomura
Muscle-specific tyrosine kinase (MuSK) antibodies are detected in a proportion of myasthenia gravis (MG) patients who are negative for acetylcholine receptor (AChR) antibodies and have prominent bulbar weakness and crises. In the MuSK ectodomains, the immunoglobulin-like 1 and 2 domains (Ig1/2) mediate the agrin-Lrp4-MuSK signaling and the cysteine-rich domain (CRD) mediates the Wnt-MuSK-Dishevelled signaling; both contribute to AChR clustering. Immunoblotting against recombinant proteins showed MuSK Ig1/2 antibodies in 33 anti-AChR-negative MG patients; 10 patients of them (30%) were additionally positive for MuSK CRD antibodies...
January 15, 2013: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/22753217/heme-oxygenase-gene-targeting-to-adipocytes-attenuates-adiposity-and-vascular-dysfunction-in-mice-fed-a-high-fat-diet
#20
Jian Cao, Stephen J Peterson, Komal Sodhi, Luca Vanella, Ignazio Barbagallo, Luigi F Rodella, Michal L Schwartzman, Nader G Abraham, Attallah Kappas
We examined the hypothesis that adipocyte dysfunction in mice fed a high-fat (HF) diet can be prevented by lentiviral-mediated and adipocyte specific-targeting delivery of the human heme oxygenase-1 (aP2-HO-1). A bolus intracardial injection of aP2-HO-1 resulted in expression of human HO-1 for up to 9.5 months. Transduction of aP2-HO-1 increased human HO-1 expression in fat tissues without affecting murine HO-1. In mice fed a HF diet, aP2-HO-1 transduction attenuated the increases in body weight, blood glucose, blood pressure, and inflammatory cytokines, as well as the content of both visceral and subcutaneous fat...
August 2012: Hypertension
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