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https://www.readbyqxmd.com/read/28518137/nerve-growth-factor-from-chinese-cobra-venom-stimulates-chondrogenic-differentiation-of-mesenchymal-stem-cells
#1
Zhenhui Lu, Danqing Lei, Tongmeng Jiang, Lihui Yang, Li Zheng, Jinmin Zhao
Growth factors such as transforming growth factor beta1 (TGF-β1), have critical roles in the regulation of the chondrogenic differentiation of mesenchymal stem cells (MSCs), which promote cartilage repair. However, the clinical applications of the traditional growth factors are limited by their high cost, functional heterogeneity and unpredictable effects, such as cyst formation. It may be advantageous for cartilage regeneration to identify a low-cost substitute with greater chondral specificity and easy accessibility...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28515680/trk-receptors-and-neurotrophin-cross-interactions-new-perspectives-toward-manipulating-therapeutic-side-effects
#2
Yazan Haddad, Vojtěch Adam, Zbyněk Heger
Some therapeutic side-effects result from simultaneous activation of homolog receptors by the same ligand. Tropomyosin receptor kinases (TrkA, TrkB and TrkC) play a major role in the development and biology of neurons through neurotrophin signaling. The wide range of cross-interactions between Trk receptors and neurotrophins vary in selectivity, affinity and function. In this study, we discuss new perspectives to the manipulation of side-effects via a better understanding of the cross-interactions at the molecular level, derived by computational methods...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28495385/derivatives-of-caffeic-acid-a-natural-antioxidant-as-the-basis-for-the-discovery-of-novel-nonpeptidic-neurotrophic-agents
#3
Fatemeh Moosavi, Razieh Hosseini, Hamid Rajaian, Tiago Silva, Diogo Magalhães E Silva, Luciano Saso, Najmeh Edraki, Ramin Miri, Fernanda Borges, Omidreza Firuzi
Neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, threaten the lives of millions of people and the number of affected patients is constantly growing with the increase of the aging population. Small molecule neurotrophic agents represent promising therapeutics for the pharmacological management of neurodegenerative diseases. In this study, a series of caffeic acid amide analogues with variable alkyl chain lengths, including ACAF3 (C3), ACAF4 (C4), ACAF6 (C6), ACAF8 (C8) and ACAF12 (C12) were synthesized and their neurotrophic activity was examined by different methods in PC12 neuronal cells...
April 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28492466/ngf-and-its-receptors-in-the-regulation-of-inflammatory-response
#4
REVIEW
Gaetana Minnone, Fabrizio De Benedetti, Luisa Bracci-Laudiero
There is growing interest in the complex relationship between the nervous and immune systems and how its alteration can affect homeostasis and result in the development of inflammatory diseases. A key mediator in cross-talk between the two systems is nerve growth factor (NGF), which can influence both neuronal cell function and immune cell activity. The up-regulation of NGF described in inflamed tissues of many diseases can regulate innervation and neuronal activity of peripheral neurons, inducing the release of immune-active neuropeptides and neurotransmitters, but can also directly influence innate and adaptive immune responses...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28490668/-trka-cking-why-no-pain-no-gain-is-the-rule-for-bone-formation
#5
Benjamin Levi
Peripheral sensory nerves expressing TrkA innervate long bones and stimulate bone formation through the Wnt/β-catenin pathway when placed under stress.
May 10, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28489355/conjugate-of-an-igg-binding-domain-with-botulinum-neurotoxin-a-lacking-the-acceptor-moiety-targets-its-snare-protease-into-trka-expressing-cells-when-coupled-to-anti-trka-igg-or-fc-%C3%AE-ngf
#6
Marc Nugent, Jiafu Wang, Gary W Lawrence, Tomas Zuraswki, Joan A Geoghegan, J Oliver Dolly
Numerous naturally-occurring toxins can perturb biological systems when they invade susceptible cells. Coupling of pertinent targeting ligands to the active domains of such proteins provides a strategy for directing these to particular cellular populations implicated in disease. A novel approach described herein involved fusion of one mutated immunoglobulin G (IgG) binding moiety of staphylococcal protein A to the SNARE protease and translocation domain of botulinum neurotoxin A (BoNT/A). This chimera could be monovalently coupled to IgG or via its Fc region to recombinant targeting ligands...
May 10, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28479141/neurodegenerative-effects-of-azithromycin-in-differentiated-pc12-cells
#7
Vicki Waetzig, Jeanette Riffert, Justus Cordt, Kirstin Reinecke, Wiebke Haeusgen, Ruwen Boehm, Ingolf Cascorbi, Thomas Herdegen
Azithromycin is a widely used macrolide antibiotic with sustained and high tissue penetration and intracellular accumulation. While short-term exposure to low-dose azithromycin is usually well tolerated, prolonged treatment can lead to unwanted neurological effects like paresthesia and hearing loss. However, the mechanism causing neurodegeneration is still unknown. Here, we show that even low therapeutically relevant azithromycin concentrations like 1µg/ml decreased cell viability by 15% and induced neurite loss of 47% after 96h in differentiated PC12 cells, which are a well-established model system for neuronal cells...
May 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28476948/hierarchical-specification-of-pruriceptors-by-runt-domain-transcription-factor-runx1
#8
Lu Qi, Chengcheng Huang, Xiaohua Wu, Yeqi Tao, Jingjing Yan, Tianyong Shi, Cheng Cao, Lu Han, Mengsheng Qiu, Qiufu Ma, Zijing Liu, Yang Liu
The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch and others. Recent genetic and single-cell RNA sequencing studies have revealed a group of DRG neurons that could be particularly relevant for acute and chronic itch information transmission. They express the natriuretic peptide type B (NPPB), as well as a cohort of receptors and neuropeptides that have been implicated in chronic itch manifestation, including the interleukin-31 receptor IL31ra and its co-receptor Osmr, the leuktriene receptor Cysltr2, somatostatin and neurotensin...
May 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28476569/design-and-synthesis-of-a-fluorinated-quinazoline-based-type-ii-trk-inhibitor-as-a-scaffold-for-pet-radiotracer-development
#9
Vadim Bernard-Gauthier, Anne Mahringer, Matthew Vesnaver, Gert Fricker, Ralf Schirrmacher
NTRK1/2/3 fusions have recently been characterized as low incidence oncogenic alterations across various tumor histologies. Tyrosine kinase inhibitors (TKIs) of the tropomyosin receptor kinase family TrkA/B/C (encoded by NTRK1/2/3) are showing promises in the clinic for the treatment of cancer patients whose diseases harbor NTRK tumor drivers. We describe herein the development of [(18)F]QMICF ([(18)F]-(R)-9), a quinazoline-based type-II pan-Trk radiotracer with nanomolar potencies for TrkA/B/C (IC50=85-650nM) and relevant TrkA fusions including TrkA-TPM3 (IC50=162nM)...
April 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28465581/nerve-growth-factor-signalling-in-pathology-and-regeneration-of-human-teeth
#10
Thimios A Mitsiadis, Henry Magloire, Pierfrancesco Pagella
Nerve growth factor (NGF) is a key regulator of the development and differentiation of neuronal and non-neuronal cells. In the present study we examined the distribution of NGF and its low and high-affinity receptors, p75(NTR) and TrkA respectively, in permanent human teeth under normal and pathological conditions. In intact functional teeth, NGF, p75(NTR) and TrkA are weakly expressed in dental pulp fibroblasts and odontoblasts that are responsible for dentine formation, while the NGF and p75(NTR) molecules are strongly expressed in nerve fibres innervating the dental pulp...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28465100/design-synthesis-and-sar-of-substituted-indoles-as-selective-trka-inhibitors
#11
Danielle M Hurzy, Darrell A Henze, Tamara D Cabalu, Kartik Narayan, Amanda Heller, Andrew J Cooke
A series of substituted indoles were examined as selective inhibitors of tropomyosin-related kinase receptor A (TrkA), a therapeutic target for the treatment of pain. An SAR optimization campaign based on ALIS screening lead compound 1 is reported.
April 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28461220/delineating-neurotrophin-3-dependent-signaling-pathways-underlying-sympathetic-axon-growth-along-intermediate-targets
#12
Austin B Keeler, Dong Suo, Juyeon Park, Christopher D Deppmann
Postganglionic sympathetic neurons detect vascular derived neurotrophin 3 (NT3) via the axonally expressed receptor tyrosine kinase, TrkA, to promote chemo-attraction along intermediate targets. Once axons arrive to their final target, a structurally related neurotrophic factor, nerve growth factor (NGF), also acts through TrkA to promote final target innervation. Does TrkA signal differently at these different locales? We previously found that Coronin-1 is upregulated in sympathetic neurons upon exposure to NGF, thereby endowing the NGF-TrkA complex with new signaling capabilities (i...
April 28, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28454094/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#13
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453662/mglur5-tunes-ngf-trka-signaling-to-orient-spiny-stellate-neuron-dendrites-toward-thalamocortical-axons-during-whisker-barrel-map-formation
#14
Jui-Yen Huang, Hui-Chen Lu
Neurons receive and integrate synaptic inputs at their dendrites, thus dendritic patterning shapes neural connectivity and behavior. Aberrant dendritogenesis is present in neurodevelopmental disorders such as Down's syndrome and autism. Abnormal glutamatergic signaling has been observed in these diseases, as has dysfunction of the metabotropic glutamate receptor 5 (mGluR5). Deleting mGluR5 in cortical glutamatergic neurons disrupted their coordinated dendritic outgrowth toward thalamocortical axons and perturbed somatosensory circuits...
April 27, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28452038/is-next-generation-sequencing-the-way-to-go-for-residual-disease-monitoring-in-acute-lymphoblastic-leukemia
#15
REVIEW
Michaela Kotrova, Jan Trka, Michael Kneba, Monika Brüggemann
Minimal residual disease (MRD) is the most important independent prognostic factor in acute lymphoblastic leukemia (ALL). Since it has been implemented into in treatment stratification strategies, cure rates have improved significantly for all age groups. Real time quantitative (RQ)-PCR of clonal immunoglobulin and T-cell receptor gene rearrangements using allele-specific primers is currently regarded as the gold standard for MRD analysis in ALL, as it is not only highly sensitive and specific but also provides accurate MRD quantification...
April 27, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28440712/gelatin-albumin-hybrid-nanoparticles-as-matrix-metalloproteinases-degradable-delivery-systems-for-breast-cancer-therapy
#16
Vahid Heravi Shargh, Hubert Hondermarck, Mingtao Liang
AIM: To develop matrix metalloproteinase-responsive gelatin-albumin hybrid nanoparticles encapsulating a selective tropomyosin receptor kinase A (TrkA) inhibitor GNF-5837 (Gel-Alb-GNF HNPs) and to demonstrate their anticancer effects in breast cancer. METHODS: Gel-Alb-GNF HNPs were prepared using a pH-controlled complexation process from cationic gelatin, dextran sulfate and albumin-bound GNF-5837. The anticancer activities of Gel-Alb-GNF HNPs were tested in a panel of subtype-specific breast cancer cell lines...
May 2017: Nanomedicine
https://www.readbyqxmd.com/read/28416686/ngf-trka-signaling-in-sensory-nerves-is-required-for-skeletal-adaptation-to-mechanical-loads-in-mice
#17
Ryan E Tomlinson, Zhi Li, Zhu Li, Liliana Minichiello, Ryan C Riddle, Arun Venkatesan, Thomas L Clemens
Sensory nerves emanating from the dorsal root extensively innervate the surfaces of mammalian bone, a privileged location for the regulation of biomechanical signaling. Here, we show that NGF-TrkA signaling in skeletal sensory nerves is an early response to mechanical loading of bone and is required to achieve maximal load-induced bone formation. First, the elimination of TrkA signaling in mice harboring mutant TrkA(F592A) alleles was found to greatly attenuate load-induced bone formation induced by axial forelimb compression...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28404842/an-immortalized-human-dorsal-root-ganglia-cell-line-provides-a-novel-context-to-study-herpes-simplex-virus-type-1-latency-and-reactivation
#18
Nikki M Thellman, Carolyn Botting, Zachary Madaj, Steven J Triezenberg
A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v-myc oncogene. In the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology and express sensory neuron-associated markers such as neurotrophin receptors TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28398601/antidepressant-imipramine-protects-bupivacaine-induced-neurotoxicity-in-dorsal-root-ganglion-neurons-through-co-activation-of-trka-and-trkb
#19
Jianrong Guo, Huan Wang, Qiang Tao, Shiyu Sun, Li Liu, Jianping Zhang, Dawei Yang
PURPOSE: In our work, we used an in vitro culture model to investigate whether antidepressant imipramine (Ip) may protect bupivacaine (Bv)-induced neurotoxicity in mouse dorsal root ganglion (DRG). METHODS: Adult mouse DRG was treated with 5 mM Bv in vitro to induce neurotoxicity. DRG was then pre-treated with Ip, prior to Bv, to examine its effects on protecting Bv-induced DRG apoptosis and neurite degeneration. Ip-induced dynamic changes in Trk receptors, including TrkA/B/C and phosphor (p-)TrkA/B/C, were examined by qPCR and western blot...
April 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28395118/etv6-runx1-like-acute-lymphoblastic-leukemia-a-novel-b-cell-precursor-leukemia-subtype-associated-with-the-cd27-cd44-immunophenotype
#20
Marketa Zaliova, Michaela Kotrova, Silvia Bresolin, Jan Stuchly, Jan Stary, Ondrej Hrusak, Geertruy Te Kronnie, Jan Trka, Jan Zuna, Martina Vaskova
We have shown previously that ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL) is distinguishable from other ALL subtypes by CD27(pos) /CD44(low-neg) immunophenotype. During diagnostic immunophenotyping of 573 childhood B-cell precursor ALL (BCP-ALL), we identified eight cases with this immunophenotype among "B-other ALL" (BCP-ALL cases negative for routinely tested chromosomal/genetic aberrations). We aimed to elucidate whether these cases belong to the recently described ETV6/RUNX1-like ALL defined by the ETV6/RUNX1-specific gene expression profile (GEP), harboring concurrent ETV6 and IKZF1 lesions...
April 10, 2017: Genes, Chromosomes & Cancer
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