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https://www.readbyqxmd.com/read/28637693/neuroblast-differentiation-during-development-and-in-neuroblastoma-requires-kif1b%C3%AE-mediated-transport-of-trka
#1
Stuart M Fell, Shuijie Li, Karin Wallis, Anna Kock, Olga Surova, Vilma Rraklli, Carolin S Höfig, Wenyu Li, Jens Mittag, Marie Arsenian Henriksson, Rajappa S Kenchappa, Johan Holmberg, Per Kogner, Susanne Schlisio
We recently identified pathogenic KIF1Bβ mutations in sympathetic nervous system malignancies that are defective in developmental apoptosis. Here we deleted KIF1Bβ in the mouse sympathetic nervous system and observed impaired sympathetic nervous function and misexpression of genes required for sympathoadrenal lineage differentiation. We discovered that KIF1Bβ is required for nerve growth factor (NGF)-dependent neuronal differentiation through anterograde transport of the NGF receptor TRKA. Moreover, pathogenic KIF1Bβ mutations identified in neuroblastoma impair TRKA transport...
May 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28632177/the-intersection-of-ngf-trka-signaling-and-amyloid-precursor-protein-processing-in-alzheimer-s-disease-neuropathology
#2
REVIEW
Nadia Canu, Giuseppina Amadoro, Viviana Triaca, Valentina Latina, Valentina Sposato, Veronica Corsetti, Cinzia Severini, Maria Teresa Ciotti, Pietro Calissano
Dysfunction of nerve growth factor (NGF) and its high-affinity Tropomyosin receptor kinase A (TrkA) receptor has been suggested to contribute to the selective degeneration of basal forebrain cholinergic neurons (BFCN) associated with the progressive cognitive decline in Alzheimer's disease (AD). The aim of this review is to describe our progress in elucidating the molecular mechanisms underlying the dynamic interplay between NGF/TrkA signaling and amyloid precursor protein (APP) metabolism within the context of AD neuropathology...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28632034/recombinant-human-nerve-growth-factor-treatment-promotes-photoreceptor-survival-in-the-retinas-of-rats-with-retinitis-pigmentosa
#3
Marta Sacchetti, Flavio Mantelli, Maria Luisa Rocco, Alessandra Micera, Laura Brandolini, Laura Focareta, Claudio Pisano, Luigi Aloe, Alessandro Lambiase
PURPOSE: Increasing evidence suggests that nerve growth factor (NGF) exerts protective effects against retinal degeneration in animal models of retinitis pigmentosa (RP). This study aims at investigating the effects of intravitreal injection of recombinant human NGF (rhNGF) on retinal photoreceptors apoptosis in an animal model of RP, the Royal College of Surgeons (RCS) rats. METHODS: Thirty-six RCS rats were treated with intravitreal injection of rhNGF or murine NGF (mNGF) or vehicle at 20 postnatal days (pd) and sacrificed at 40 pd...
March 1, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28625641/emergence-of-novel-and-dominant-acquired-egfr-solvent-front-mutations-at-gly796-g796s-r-together-with-c797s-r-and-l792f-h-mutations-in-one-egfr-l858r-t790m-nsclc-patient-who-progressed-on-osimertinib
#4
Sai-Hong Ignatius Ou, Jean Cui, Alexa B Schrock, Michael E Goldberg, Viola W Zhu, Lee Albacker, Philip J Stephens, Vincent A Miller, Siraj M Ali
Acquired epidermal growth factor receptor (EGFR) resistance mutations to osimertinib are common, including the EGFR C797S that abolishes the covalent binding of osimertinib to EGFR. Here we report the emergence of novel EGFR solvent front mutations at Gly796 (G796S/R) in addition to a hinge pocket L792F/H mutations, and C797S/G all in cis with T790M in a single patient on progression on osimertinib as detected by plasma circulating tumor DNA (ctDNA) assay in the course of clinical care. A 69-year-old Caucasian female former light-smoker presented with stage IV EGFR L858R positive adenocarcinoma who developed EGFR T790M mutation after 8 month treatment of erlotinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28604655/brain-derived-neurotrophic-factor-tropomyosin-related-kinase-b-signaling-pathway-contributes-to-the-aggressive-behavior-of-lung-squamous-cell-carcinoma
#5
Keigo Ozono, Yoshihiro Ohishi, Hideya Onishi, Katsuya Nakamura, Junichi Motoshita, Masato Kato, Ryoichi Nakanishi, Masafumi Nakamura, Yoshinao Oda
The tropomyosin-related kinase (Trk) family consists of TrkA, TrkB, and TrkC, which play essential roles in tumor progression and/or suppression in various cancers. Little is known about the biological significance of the Trk family in human lung squamous cell carcinoma (SCC). Here we investigated the clinical significance of the protein expression of Trk family members in samples from 99 SCC patients, and we explored the relationship between invasion/proliferation activities and Trk expression using lung SCC cell lines to clarify the biological significance of the Trk family in lung SCC...
June 12, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28589908/activation-of-trka-receptor-elicits-mastocytosis-in-mice-and-is-involved-in-the-development-of-resistance-to-kit-targeted-therapy
#6
Min Yang, Zengkai Pan, Kezhi Huang, Guntram Büsche, Friedrich Feuerhake, Anuhar Chaturvedi, Danian Nie, Michael Heuser, Felicitas Thol, Nils von Neuhoff, Arnold Ganser, Zhixiong Li
The neurotrophins (NTs) play a key role in neuronal survival and maintenance. The TRK (tropomyosin-related kinase) tyrosine kinase receptors (TRKA, TRKB, TRKC) are high affinity receptors for NTs. There is increasing data demonstrating an important role of the TRK family in cancer initiation and progression. NTs have been known for many years to promote chemotaxis, maturation, and survival of mast cells. However, the role of NT signaling in the pathogenesis of mastocytosis is not well understood. In this study, we demonstrate that activation of TRKA by its ligand nerve growth factor (NGF) is potent to trigger a disease in mice with striking similarities to human systemic mastocytosis (SM)...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571657/transplantation-of-bone-marrow-stromal-stem-cells-overexpressing-tropomyosin-receptor-kinase-a-for-peripheral-nerve-repair
#7
Meige Zheng, Junxiu Duan, Zhendan He, Zhiwei Wang, Shuhua Mu, Zhiwen Zeng, Junle Qu, Dong Wang, Jian Zhang
BACKGROUND AIMS: Previously we reported that overexpression of tropomyosin receptor kinase A (TrkA) could improve the survival and Schwann-like cell differentiation of bone marrow stromal stem cells (BMSCs) in nerve grafts for bridging rat sciatic nerve defects. The aim of this study was to investigate how TrkA affects the efficacy of BMSCs transplantation on peripheral nerve regeneration and functional recovery. METHODS: Rat BMSCs were infected with recombinant lentiviruses to construct TrkA-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then seeded in acellular nerve allografts for bridging 10-mm rat sciatic nerve defects...
May 29, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28567989/the-novel-synthetic-microneurotrophin-bnn27-protects-mature-oligodendrocytes-against-cuprizone-induced-death-through-the-ngf-receptor-trka
#8
Giulia Bonetto, Ioannis Charalampopoulos, Achille Gravanis, Domna Karagogeos
BNN27, a member of a chemical library of C17-spiroepoxy derivatives of the neurosteroid DHEA, has been shown to regulate neuronal survival through its selective interaction with NGF receptors (TrkA and p75(NTR) ), but its role on glial populations has not been studied. Here, we present evidence that BNN27 provides trophic action (rescue from apoptosis), in a TrkA-dependent manner, to mature oligodendrocytes when they are challenged with the cuprizone toxin in culture. BNN27 treatment also increases oligodendrocyte maturation and diminishes microglia activation in vitro...
August 2017: Glia
https://www.readbyqxmd.com/read/28557340/trka-is-a-binding-partner-of-npm-alk-that-promotes-the-survival-of-alk-t-cell-lymphoma
#9
Wenyu Shi, Suraj Konnath George, Bhawana George, Choladda V Curry, Albina Murzabdillaeva, Serhan Alkan, Hesham M Amin
Nucleophosmin-anaplastic lymphoma kinase-expressing (NPM-ALK(+) ) T-cell lymphoma is an aggressive neoplasm that is more commonly seen in children and young adults. The pathogenesis of NPM-ALK(+) T-cell lymphoma is not completely understood. It is characterized by the expression of the chimeric tyrosine kinase NPM-ALK. Wild-type ALK is a receptor tyrosine kinase that is physiologically expressed in neural tissues during early stages of human development, which suggests that ALK may interact with neurotrophic factors...
May 30, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28554249/suppression-of-asparaginyl-endopeptidase-attenuates-breast-cancer-induced-bone-pain-through-inhibition-of-neurotrophin-receptors
#10
Peng Yao, Yuanyuan Ding, Zhenkai Han, Ying Mu, Tao Hong, Yongqiang Zhu, Hongxi Li
Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28543763/7-8-3-trihydroxyflavone-protects-h-r-induced-apoptosis-and-induces-in-vivo-growth-of-human-embryonic-stem-cell-derived-cardiomyocytes
#11
Jiaxiang Li, Cuiping Wang, Bao Zhang Baiyun Tang
BACKGROUND: Cellular therapy of human embryonic stem cell-derived cardiomyocytes (hES-CMs) holds great promise for regenerating infarcted cardiac tissues. Yet, the major challenge remains as little cells survived after grafting. In this study, we examined whether treating hES-CMs with 7, 8, 3'-Trihydroxyflavone (THF) may improve hES-CMs developments both in vitro and in vivo. METHOD: HES-CMs were differentiated in vitro, and treated with 5 μ59M THF for 24 h...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28518137/nerve-growth-factor-from-chinese-cobra-venom-stimulates-chondrogenic-differentiation-of-mesenchymal-stem-cells
#12
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
#13
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
#14
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
#15
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
#16
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
#17
Marc Nugent, Jiafu Wang, Gary Lawrence, Tomas Zurawski, 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...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28479141/neurodegenerative-effects-of-azithromycin-in-differentiated-pc12-cells
#18
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
#19
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
#20
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)...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
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