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https://www.readbyqxmd.com/read/28814877/mechanism-and-therapeutic-effectiveness-of-nerve-growth-factor-in-osteoarthritis-pain
#1
REVIEW
Xiushuai Shang, Zhaofei Wang, Hairong Tao
Osteoarthritis (OA) is the most common form of articular joint arthritis and a cause of significant morbidity. In this review, we present the role of nerve growth factor (NGF) in pain generation, relationship between NGF and OA pain, and pathogenic factors (interleukin-1β, transforming growth factor-β1, mechanical loading, and adipokines) involved in OA development. Since NGF blocking is an efficient way to inhibit OA-associated pain, we summarize four categories of drugs that target NGF/tropomyosin receptor kinase A (TrkA) signaling...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28814511/targeting-phospholipase-d4-attenuates-kidney-fibrosis
#2
Priyanka Trivedi, Ramya K Kumar, Ashwin Iyer, Sarah Boswell, Casimiro Gerarduzzi, Vivekkumar P Dadhania, Zach Herbert, Nikita Joshi, James P Luyendyk, Benjamin D Humphreys, Vishal S Vaidya
Phospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury...
August 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28803853/developmental-suppression-of-forebrain-trka-receptors-and-attentional-capacities-in-aging-rats-a-longitudinal-study
#3
Brittney Yegla, Vinay Parikh
Basal forebrain (BF) cholinergic neurons innervating the cortex regulate cognitive, specifically attentional, processes. Cholinergic atrophy and cognitive decline occur at an accelerated pace in age-related neurodegenerative disorders such as Alzheimer's disease; however, the mechanism responsible for this phenomenon remains unknown. Here we hypothesized that developmental suppression of nerve growth factor signaling, mediated via tropomyosin-related kinase A (trkA) receptors, would escalate age-related attentional vulnerability...
August 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28800073/electronegative-low-density-lipoprotein-l5-impairs-viability-and-ngf-induced-neuronal-differentiation-of-pc12-cells-via-lox-1
#4
Jiz-Yuh Wang, Chiou-Lian Lai, Ching-Tien Lee, Chen-Yen Lin
There have been striking associations of cardiovascular diseases (e.g., atherosclerosis) and hypercholesterolemia with increased risk of neurodegeneration including Alzheimer's disease (AD). Low-density lipoprotein (LDL), a cardiovascular risk factor, plays a crucial role in AD pathogenesis; further, L5, a human plasma LDL fraction with high electronegativity, may be a factor contributing to AD-type dementia. Although L5 contributing to atherosclerosis progression has been studied, its role in inducing neurodegeneration remains unclear...
August 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28796418/role-of-the-gm1-ganglioside-oligosaccharide-portion-in-the-trka-dependent-neurite-sprouting-in-neuroblastoma-cells
#5
Elena Chiricozzi, Diego Yuri Pomè, Margherita Maggioni, Erika Di Biase, Chiara Parravicini, Luca Palazzolo, Nicoletta Loberto, Ivano Eberini, Sandro Sonnino
GM1 ganglioside (II(3) NeuAc-Gg4 Cer) is known to promote neurite formation in neuroblastoma cells by activating TrkA-MAPK pathway. The molecular mechanism by which GM1 is involved in the neurodifferentiation process is still unknown, however, in vitro and in vivo evidences have suggested that the oligosaccharide portion of this ganglioside could be involved. Here, we report that, similarly to the entire GM1 molecule, its oligosaccharide II(3) NeuAc-Gg4, rather than its ceramide (Cer) portion is responsible for the neurodifferentiation process by augmenting neurite elongation and increasing the neurofilament protein expression in murine neuroblastoma cells, Neuro2a...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28793172/tropomyosin-receptor-kinase-a-expression-on-merkel-cell-carcinoma-cells
#6
Ulrike Wehkamp, Sophie Stern, Sandra Krüger, Axel Hauschild, Christoph Röcken, Friederike Egberts
Importance: Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor frequently associated with the Merkel cell polyomavirus. Immune checkpoint therapy showed remarkable results, although not all patients are responsive to this therapy. Anti-tropomyosin receptor kinase A (TrkA)-targeted treatment has shown promising results in several tumor entities. Objective: To determine TrkA expression in MCC as a rationale for potential targeted therapy. Design, Setting, and Participants: This case series study investigated the MCC specimens of 55 patients treated at the Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany, from January 1, 2005, through December 31, 2015...
August 9, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28791558/zar1-knockdown-promotes-the-differentiation-of-human-neuroblastoma-cells-by-suppression-of-mycn-expression
#7
Yosuke Watanabe, Yoshiaki Ishizuka, Takayuki Hirano, Eri Nagasaki-Maeoka, Reina Hoshi, Shinsuke Yoshizawa, Shota Uekusa, Hiroyuki Kawashima, Kiminobu Sugito, Kenichi Shinohara, Noboru Fukuda, Hiroki Nagase, Masayoshi Soma, Tsugumichi Koshinaga, Kyoko Fujiwara
Although DNA hypermethylation at non-promoter region of the Zygote arrest 1 (ZAR1) gene has been observed in many types of tumor, including neuroblastoma (NB), the role of this gene in tumor development and/or progression is unclear. One reason is that knowledge about the function of ZAR1 protein is limited. Although it has been reported that ZAR1 plays a crucial role in early embryogenesis and may act as a transcriptional repressor for some transcripts, the detailed mechanism is still elusive. In the present study, we analyzed public data of NB patients and found that higher expression levels of ZAR1 were significantly associated with a shorter survival period...
August 8, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28767387/identification-and-characterization-of-a-novel-scyl3-ntrk1-rearrangement-in-a-colorectal-cancer-patient
#8
Massimo Milione, Elena Ardini, Jason Christiansen, Emanuele Valtorta, Silvio Veronese, Roberta Bosotti, Alessio Pellegrinelli, Adele Testi, Filippo Pietrantonio, Giovanni Fucà, Ge Wei, Danielle Murphy, Salvatore Siena, Antonella Isacchi, Filippo De Braud
In colorectal cancer patients, chromosomal rearrangements involving NTRK1 gene (encoding the TRKA protein) are shown in a small subset of patients and are associated with the constitutive activation of the kinase domain of TRKA. In turn, activated TRKA-fusion proteins are associated with proliferation and survival in colorectal cancer tumors.Here we report the identification and functional characterization of a new SCYL3-NTRK1 fusion gene in a 61-year-old colorectal cancer patient. To our knowledge, this fusion protein has never been previously documented in oncological patients...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28758954/chemical-constituents-from-hericium-erinaceus-promote-neuronal-survival-and-potentiate-neurite-outgrowth-via-the-trka-erk1-2-pathway
#9
Cheng-Chen Zhang, Chen-Yu Cao, Miwa Kubo, Kenichi Harada, Xi-Tao Yan, Yoshiyasu Fukuyama, Jin-Ming Gao
Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6) and one new natural product (2) together with five known compounds (1,3-5,7) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28749040/retraction-microrna-4656-is-a-prognostic-factor-and-tumor-suppressor-in-human-pancreatic-cancer-through-a-downstream-target-of-trka-by-xianglong-tan-jinyong-lv-guodong-zhao-zhiming-zhao-chenggang-li-yong-xu-and-minggen-hu
#10
https://www.readbyqxmd.com/read/28744222/presence-of-functional-neurotrophin-trkb-receptors-in-the-rat-superior-cervical-ganglion
#11
Pablo Valle-Leija, Angeles Cancino-Rodezno, Berardo M Sánchez-Tafolla, Erwin Arias, Diana Elinos, Jessica Feria, María E Zetina, Miguel A Morales, Fredy Cifuentes
Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non-functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) modulate synaptic transmission and synaptic plasticity in neurons of the superior cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in sympathetic ganglia and contributes to the effects of BDNF upon sympathetic function, we characterized the presence and activity of the neurotrophin receptors expressed in the adult SCG compared with their presence in neonatal and cultured sympathetic neurons...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28742111/axonal-outgrowth-neuropeptides-expression-and-receptors-tyrosine-kinase-phosphorylation-in-3d-organotypic-cultures-of-adult-dorsal-root-ganglia
#12
Estrela Neto, Cecília J Alves, Luís Leitão, Daniela M Sousa, Inês S Alencastre, Francisco Conceição, Meriem Lamghari
Limited knowledge from mechanistic studies on adult sensory neuronal activity was generated, to some extent, in recapitulated adult in vivo 3D microenvironment. To fill this gap there is a real need to better characterize the adult dorsal root ganglia (aDRG) organotypic cultures to make these in vitro systems exploitable for different approaches, ranging from basic neurobiology to regenerative therapies, to address the sensory nervous system in adult stage. We conducted a direct head-to-head comparison of aDRG and embryonic DRG (eDRG) organotypic culture focusing on axonal growth, neuropeptides expression and receptors tyrosine kinase (RTK) activation associated with neuronal survival, proliferation and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28739680/bdnf-an-oncogene-or-tumor-suppressor
#13
REVIEW
Daniel P Radin, Parth Patel
Neurotrophins are a family of growth factors that are vital to the proper development of the central nervous system. Their effects on cells are governed by the expression and activation of the tyrosine kinase receptors TrkA, TrkB and TrkC. TrkB has been immensely implicated in mediating neuronal migration, development and differentiation. It has also been shown to protect several neuronal cell types from an array of cytotoxic stressors after activation by its conjugate ligand brain-derived neurotrophic factor (BDNF)...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28710024/intranasal-nerve-growth-factor-attenuating-the-seizure-onset-via-p75r-caspase-pathway-in-the-experimental-epilepsy
#14
Jing'an Lei, Fang Feng, Yuanyuan Duan, Feng Xu, Zhiguang Liu, Lifei Lian, Qiming Liang, Na Zhang, Furong Wang
BACKGROUND: Nerve growth factor (NGF) shows neuroprotection while it is hard to cross the blood-brain barrier due to its large molecular weight. Our study used intranasal delivery of NGF to treat the experimental epilepsy. METHODS: The seizure was induced by injection of pentylenetetrazol (40mg/kg) into the rat. Based on the behavior performance, the successful models were randomized into control and NGF groups, given medium or NGF intranasally, respectively. The onset and duration of seizure were recorded...
July 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28708822/an-ancient-neurotrophin-receptor-code-a-single-runx-cbf%C3%AE-complex-determines-somatosensory-neuron-fate-specification-in-zebrafish
#15
Philia Gau, Andrew Curtright, Logan Condon, David W Raible, Ajay Dhaka
In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28708379/chemical-genomics-structure-elucidation-and-in-vivo-studies-of-the-marine-derived-anticlostridial-ecteinamycin
#16
Thomas P Wyche, René F Ramos Alvarenga, Jeff S Piotrowski, Megan N Duster, Simone R Warrack, Gabriel Cornilescu, Travis J De Wolfe, Yanpeng Hou, Doug R Braun, Gregory A Ellis, Scott W Simpkins, Justin Nelson, Chad L Myers, James Steele, Hirotada Mori, Nasia Safdar, John L Markley, Scott R Rajski, Tim S Bugni
A polyether antibiotic, ecteinamycin (1), was isolated from a marine Actinomadura sp., cultivated from the ascidian Ecteinascidia turbinata. (13)C enrichment, high resolution NMR spectroscopy, and molecular modeling enabled elucidation of the structure of 1, which was validated on the basis of comparisons with its recently reported crystal structure. Importantly, ecteinamycin demonstrated potent activity against the toxigenic strain of Clostridium difficile NAP1/B1/027 (MIC = 59 ng/μL), as well as other toxigenic and nontoxigenic C...
July 26, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28701747/neap-dusp26-suppresses-receptor-tyrosine-kinases-and-regulates-neuronal-development-in-zebrafish
#17
Chi-Hwa Yang, Yu-Jung Yeh, Jiz-Yuh Wang, Ya-Wen Liu, Yen-Lin Chen, Hui-Wen Cheng, Chun-Mei Cheng, Yung-Jen Chuang, Chiou-Hwa Yuh, Yi-Rong Chen
Expression of neuroendocrine-associated phosphatase (NEAP, also named as dual specificity phosphatase 26, [DUSP26]) is restricted to neuroendocrine tissues. We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells upon NGF stimulation. Conversely, suppressing NEAP expression by RNA interference enhanced TrkA and FGFR1 phosphorylation. NEAP was capable of de-phosphorylating TrkA and FGFR1 directly in vitro...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701730/the-mll-recombinome-of-acute-leukemias-in-2017
#18
C Meyer, T Burmeister, D Gröger, G Tsaur, L Fechina, S Renneville, R Sutton, N C Venn, M Emerenciano, M S Pombo-de-Oliveira, C Barbieri Blunck, B Almeida Lopes, J Zuna, J Trka, P Ballerini, H Lapillonne, M De Braekeleer, G Cazzaniga, L Corral Abascal, V H J van der Velden, E Delabesse, T S Park, S H Oh, M L M Silva, T Lund-Aho, V Juvonen, A S Moore, O Heidenreich, J Vormoor, E Zerkalenkova, Y Olshanskaya, C Bueno, P Menendez, S Teigler-Schlegel, U Zur Stadt, J Lentes, G Göhring, S Kustanovich, O Aleinikova, B W Schäfer, S Kubetzko, H O Madsen, B Gruhn, X Duarte, P Gameiro, E Lippert, S Bidet, J M Cayuela, E Clappier, C N Alonso, C M Zwaan, M M van den Heuvel-Eibrink, S Izraeli, L Trakhtenbrot, P Archer, J Hancock, A Möricke, J Alten, M Schrappe, M Stanulla, S Strehl, A Attarbaschi, M Dworzak, O A Haas, R Panzer-Grümayer, L Sedék, T Szczepański, S Caye, L Suarez, H Cavé, R Marschalek
Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here, we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements habe been identified so far, of which 94 TPGs are now characterized at the molecular level. Thirty-five out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene...
July 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28701524/nanoparticles-increase-human-bronchial-epithelial-cell-susceptibility-to-respiratory-syncytial-virus-infection-via-nerve-growth-factor-induced-autophagy
#19
Sreeparna Chakraborty, Vincent Castranova, Miriam K Perez, Giovanni Piedimonte
Cytotoxic and neuroinflammatory effects of TiO2 nanoparticles (TiO2-NP) in human airways are mediated by nerve growth factor (NGF), which is also implicated in the pathophysiology of respiratory syncytial virus (RSV) infection. We tested the hypothesis that exposure to TiO2-NP results in increased susceptibility to RSV infection and exacerbation of airway inflammation via NGF-mediated induction of autophagy in lower respiratory tract cells. Human primary bronchial epithelial cells were exposed to TiO2-NP for 24 h prior to infection with recombinant red RSV (rrRSV)...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28696690/a-kinome-wide-selective-radiolabeled-trkb-c-inhibitor-for-in-vitro-and-in-vivo-neuroimaging-synthesis-preclinical-evaluation-and-first-in-human
#20
Vadim Bernard-Gauthier, Justin J Bailey, Andrew V Mossine, Simon Klaus Lindner, Lena Vomacka, Arturo Aliaga, Xia Shao, Carole A Quesada, Phillip S Sherman, Anne Mahringer, Alexey Kostikov, Marilyn Grand'Maison, Pedro Rosa-Neto, Jean-Paul Soucy, Alexander Thiel, David R Kaplan, Gert Fricker, Björn Wängler, Peter Bartenstein, Ralf Schirrmacher, Peter J H Scott
The proto-oncogenes NTRK1/2/3 encode the tropomyosin receptor kinases TrkA/B/C which play pivotal roles in neurobiology and cancer. We describe herein the discovery of [(11)C]-(R)-3 ([(11)C]-(R)-IPMICF16), a first-in-class positron emission tomography (PET) TrkB/C-targeting radiolabeled kinase inhibitor lead. Relying on extensive human kinome vetting, we show that (R)-3 is the most potent and most selective TrkB/C inhibitor characterized to date. It is demonstrated that [(11)C]-(R)-3 readily crosses the blood-brain barrier (BBB) in rodents and selectively binds to TrkB/C receptors in vivo, as evidenced by entrectinib blocking studies...
July 11, 2017: Journal of Medicinal Chemistry
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