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https://www.readbyqxmd.com/read/27891557/exogenous-expression-of-nt-3-and-trkc-genes-in-bone-marrow-stromal-cells-elevated-the-survival-rate-of-the-cells-in-the-course-of-neural-differentiation
#1
Houri Edalat, Zahra Hajebrahimi, Vahid Pirhajati, Mahmoud Tavallaei, Mansoureh Movahedin, Seyed Javad Mowla
Bone marrow stromal cells (BMSCs) are attractive cellular sources for cell therapy of many diseases, specifically neurodegenerative ones. The potential capability of BMSCs could be further augmented by enhancing their neuroprotective property, differentiation potential, and survival rate subsequent to transplantation. Therefore, a concurrent upregulation of neurotrophin-3 (NT-3) and its high affinity receptor, tyrosin kinase C (TrkC), was utilized in our study. BMSCs were cotransfected with pDsRed1-N1-NT-3 and pCMX-TrkC plasmids before induction of neural differentiation...
November 28, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27853305/tropomyosin-receptor-kinase-c-targeted-delivery-of-a-peptidomimetic-ligand-photosensitizer-conjugate-induces-antitumor-immune-responses-following-photodynamic-therapy
#2
Chin Siang Kue, Anyanee Kamkaew, Siew Hui Voon, Lik Voon Kiew, Lip Yong Chung, Kevin Burgess, Hong Boon Lee
Tropomyosin receptor kinase C (TrkC) targeted ligand-photosensitizer construct, IYIY-diiodo-boron-dipyrromethene (IYIY-I2-BODIPY) and its scrambled counterpart YIYI-I2-BODIPY have been prepared. IYIY-I2-BODIPY binds TrkC similar to neurotrophin-3 (NT-3), and NT-3 has been reported to modulate immune responses. Moreover, it could be shown that photodynamic therapy (PDT) elevates antitumor immune responses. This prompted us to investigate the immunological impacts mediated by IYIY-I2-BODIPY in pre- and post-PDT conditions...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27843590/ntrk-gene-fusions-as-novel-targets-of-cancer-therapy-across-multiple-tumour-types
#3
REVIEW
Alessio Amatu, Andrea Sartore-Bianchi, Salvatore Siena
The tropomyosin receptor kinase (Trk) receptor family comprises 3 transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors that are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue and play an essential role in the physiology of development and function of the nervous system through activation by neurotrophins. Gene fusions involving NTRK genes lead to transcription of chimeric Trk proteins with constitutively activated or overexpressed kinase function conferring oncogenic potential...
2016: ESMO Open
https://www.readbyqxmd.com/read/27830679/-effects-of-ischemia-on-the-expression-of-neurotrophins-and-their-receptors-in-rat-brain-structures-outside-the-lesion-site-including-on-the-opposite-hemisphere
#4
V G Dmitrieva, V V Stavchansky, O V Povarova, V I Skvortsova, S A Limborska, L V Dergunova
Neurotrophins stimulate the regeneration of neural tissue after lesions. It is also known that the sources of neurogenesis and cerebral function recovery are predominantly located in subcortical brain structures. The effects of ischemia on the expression of genes that encode neurotrophins (Bdnf, Ngf, Nt-3) and their receptors (TrkB, TrkA, TrkC, p75) in brain structures outside the lesion site were studied 3, 24, and 72 h after irreversible unilateral occlusion of the middle cerebral artery in rats. Changes in the mRNA expression of these genes were assessed by relative quantification using real-time RT-PCR...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27775476/alteration-of-selected-neurotrophic-factors-and-their-receptor-expression-in-mouse-brain-response-to-whole-brain-irradiation
#5
Ewa Pius-Sadowska, Miłosz Piotr Kawa, Patrycja Kłos, Dorota Rogińska, Michał Rudnicki, Boehlke Marek, Piotr Waloszczyk, Bogusław Machaliński
Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase...
October 24, 2016: Radiation Research
https://www.readbyqxmd.com/read/27697534/emerging-roles-of-the-neurotrophin-receptor-trkc-in-synapse-organization
#6
Yusuke Naito, Alfred Kihoon Lee, Hideto Takahashi
Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ)...
September 30, 2016: Neuroscience Research
https://www.readbyqxmd.com/read/27695040/the-paradoxical-signals-of-two-trkc-receptor-isoforms-supports-a-rationale-for-novel-therapeutic-strategies-in-als
#7
Fouad Brahimi, Mario Maira, Pablo F Barcelona, Alba Galan, Tahar Aboulkassim, Katrina Teske, Mary-Louise Rogers, Lisa Bertram, Jing Wang, Masoud Yousefi, Robert Rush, Marc Fabian, Neil Cashman, H Uri Saragovi
Full length TrkC (TrkC-FL) is a receptor tyrosine kinase whose mRNA can be spliced to a truncated TrkC.T1 isoform lacking the kinase domain. Neurotrophin-3 (NT-3) activates TrkC-FL to maintain motor neuron health and function and TrkC.T1 to produce neurotoxic TNF-α; hence resulting in opposing pathways. In mouse and human ALS spinal cord, the reduction of miR-128 that destabilizes TrkC.T1 mRNA results in up-regulated TrkC.T1 and TNF-α in astrocytes. We exploited conformational differences to develop an agonistic mAb 2B7 that selectively activates TrkC-FL, to circumvent TrkC...
2016: PloS One
https://www.readbyqxmd.com/read/27688482/impact-of-aging-on-proprioceptive-sensory-neurons-and-intrafusal-muscle-fibers-in-mice
#8
Sydney K Vaughan, Olivia L Stanley, Gregorio Valdez
The impact of aging on proprioceptive sensory neurons and intrafusal muscle fibers (IMFs) remains largely unexplored despite the central function these cells play in modulating voluntary movements. Here, we show that proprioceptive sensory neurons undergo deleterious morphological changes in middle age (11- to 13-month-old) and old (15- to 21-month-old) mice. In the extensor digitorum longus and soleus muscles of middle age and old mice, there is a significant increase in the number of Ia afferents with large swellings that fail to properly wrap around IMFs compared with young adult (2- to 4-month-old) mice...
September 29, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27665078/transplantation-of-tissue-engineering-neural-network-and-formation-of-neuronal-relay-into-the-transected-rat-spinal-cord
#9
Bi-Qin Lai, Ming-Tian Che, Bao-Ling Du, Xiang Zeng, Yuan-Huan Ma, Bo Feng, Xue-Chen Qiu, Ke Zhang, Shu Liu, Hui-Yong Shen, Jin-Lang Wu, Eng-Ang Ling, Yuan-Shan Zeng
Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co-culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection...
December 2016: Biomaterials
https://www.readbyqxmd.com/read/27540475/recent-advances-in-understanding-neurotrophin-signaling
#10
REVIEW
Mark Bothwell
The nerve growth factor family of growth factors, collectively known as neurotrophins, are evolutionarily ancient regulators with an enormous range of biological functions. Reflecting this long history and functional diversity, mechanisms for cellular responses to neurotrophins are exceptionally complex. Neurotrophins signal through p75 (NTR), a member of the TNF receptor superfamily member, and through receptor tyrosine kinases (TrkA, TrkB, TrkC), often with opposite functional outcomes. The two classes of receptors are activated preferentially by proneurotrophins and mature processed neurotrophins, respectively...
2016: F1000Research
https://www.readbyqxmd.com/read/27511117/experimental-verification-of-a-predicted-novel-microrna-located-in-human-pik3ca-gene-with-a-potential-oncogenic-function-in-colorectal-cancer
#11
Ali Jason Saleh, Bahram M Soltani, Sadat Dokanehiifard, Abdallah Medlej, Mahmoud Tavalaei, Seyed Javad Mowla
PI3K/AKT signaling is involved in cell survival, proliferation, and migration. In this pathway, PI3Kα enzyme is composed of a regulatory protein encoded by p85 gene and a catalytic protein encoded by PIK3CA gene. Human PIK3CA locus is amplified in several cancers including lung and colorectal cancer (CRC). Therefore, microRNAs (miRNAs) that are encoded within the PIK3CA gene might have a role in cancer development. Here, we report a novel microRNA named PIK3CA-miR1 (EBI accession no. LN626315), which is located within PIK3CA gene...
August 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27334657/a-small-molecule-trkb-trkc-neurotrophin-receptor-co-activator-with-distinctive-effects-on-neuronal-survival-and-process-outgrowth
#12
Tao Yang, Stephen M Massa, Kevin C Tran, Danielle A Simmons, Jayakumar Rajadas, Anne Y Zeng, Taichang Jang, Sara Carsanaro, Frank M Longo
Neurotrophin (NT) receptors are coupled to numerous signaling networks that play critical roles in neuronal survival and plasticity. Several non-peptide small molecule ligands have recently been reported that bind to and activate specific tropomyosin-receptor kinase (Trk) NT receptors, stimulate their downstream signaling, and cause biologic effects similar to, though not completely overlapping, those of the native NT ligands. Here, in silico screening, coupled with low-throughput neuronal survival screening, identified a compound, LM22B-10, that, unlike prior small molecule Trk ligands, binds to and activates TrkB as well as TrkC...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27318978/indole-like-trk-receptor-antagonists
#13
Jaana Tammiku-Taul, Rahel Park, Kaur Jaanson, Kristi Luberg, Dimitar A Dobchev, Dzmitry Kananovich, Artur Noole, Merle Mandel, Allen Kaasik, Margus Lopp, Tõnis Timmusk, Mati Karelson
The virtual screening for new scaffolds for TrkA receptor antagonists resulted in potential low molecular weight drug candidates for the treatment of neuropathic pain and cancer. In particular, the compound (Z)-3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxindole and its derivatives were assessed for their inhibitory activity against Trk receptors. The IC50 values were computationally predicted in combination of molecular and fragment-based QSAR. Thereafter, based on the structure-activity relationships (SAR), a series of new compounds were designed and synthesized...
October 4, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27235870/neurotrophins-and-specific-receptors-in-the-oviduct-tracts-of-japanese-quail-coturnix-coturnix-japonica
#14
L Maruccio, L Castaldo, L D'Angelo, C Gatta, C Lucini, C Cotea, C Solcan, E L Nechita
Neurotrophins (NGF, BDNF and NT-3) and their specific receptors (TrkA, TrkB and TrkC) were studied in the oviduct of egg laying quails. Neurotrophins (NTs) are mainly involved in the development and maintenance of neuronal populations in the central and peripheral nervous system, but also in reproductive system. In this survey, we first studied the morphological organization of the quail oviduct, distinguished in infundibulum, magnum, isthmus, uterus and vagina, and then we analyzed the expression and localization of NTs and Trks receptors in the whole tracts...
May 25, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27197756/neurotrophins-and-their-trk-receptors-in-the-cerebellum-of-zebrafish
#15
Claudia Gatta, Gennaro Altamura, Luigi Avallone, Luciana Castaldo, Annunziata Corteggio, Livia D'Angelo, Paolo de Girolamo, Carla Lucini
Neurotrophins (NTs) and their specific Trk-receptors are key molecules involved in the regulation of survival, proliferation, and differentiation of central nervous system during development and adulthood in vertebrates. In the present survey, we studied the expression and localization of neurotrophins and their Trk-receptors in the cerebellum of teleost fish Danio rerio (zebrafish). Teleostean cerebellum is composed of a valvula, body and vestibulolateral lobe. Valvula and body show the same three-layer structure as cerebellar cortex in mammals...
June 2016: Journal of Morphology
https://www.readbyqxmd.com/read/27167968/neurotrophins-and-specific-receptors-in-the-oviduct-tracts-of-japanese-quail-coturnix-coturnix-japonica
#16
L Maruccio, L Castaldo, L D'Angelo, C Gatta, C Lucini, C Cotea, C Solcan, E L Nechita
Neurotrophins (NGF, BDNF and NT-3) and their specific receptors (TrkA, TrkB and TrkC) were studied in the oviduct of egg laying quails. Neurotrophins (NTs) are mainly involved in the development and maintenance of neuronal populations in the central and peripheral nervous system, but also in reproductive system. In this survey, we first studied the morphological organization of the quail oviduct, distinguished in infundibulum, magnum, isthmus, uterus and vagina, and then we analyzed the expression and localization of NTs and Trks receptors in the whole tracts...
September 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27122038/neurotrophin-3-regulates-synapse-development-by-modulating-trkc-ptp%C3%AF-synaptic-adhesion-and-intracellular-signaling-pathways
#17
Kyung Ah Han, Doyeon Woo, Seungjoon Kim, Gayoung Choii, Sangmin Jeon, Seoung Youn Won, Ho Min Kim, Won Do Heo, Ji Won Um, Jaewon Ko
UNLABELLED: Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ...
April 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27076431/merkel-cell-driven-bdnf-signaling-specifies-sai-neuron-molecular-and-electrophysiological-phenotypes
#18
Erin G Reed-Geaghan, Margaret C Wright, Lauren A See, Peter C Adelman, Kuan Hsien Lee, H Richard Koerber, Stephen M Maricich
UNLABELLED: The extent to which the skin instructs peripheral somatosensory neuron maturation is unknown. We studied this question in Merkel cell-neurite complexes, where slowly adapting type I (SAI) neurons innervate skin-derived Merkel cells. Transgenic mice lacking Merkel cells had normal dorsal root ganglion (DRG) neuron numbers, but fewer DRG neurons expressed the SAI markers TrkB, TrkC, and Ret. Merkel cell ablation also decreased downstream TrkB signaling in DRGs, and altered the expression of genes associated with SAI development and function...
April 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27028240/detecting-gene-rearrangements-in-patient-populations-through-a-2-step-diagnostic-test-comprised-of-rapid-ihc-enrichment-followed-by-sensitive-next-generation-sequencing
#19
Danielle A Murphy, Heather A Ely, Robert Shoemaker, Aaron Boomer, Brady P Culver, Ian Hoskins, Josh D Haimes, Ryan D Walters, Diane Fernandez, Joshua A Stahl, Jeeyun Lee, Kyoung-Mee Kim, Jennifer Lamoureux, Jason Christiansen
Targeted therapy combined with companion diagnostics has led to the advancement of next-generation sequencing (NGS) for detection of molecular alterations. However, using a diagnostic test to identify patient populations with low prevalence molecular alterations, such as gene rearrangements, poses efficiency, and cost challenges. To address this, we have developed a 2-step diagnostic test to identify NTRK1, NTRK2, NTRK3, ROS1, and ALK rearrangements in formalin-fixed paraffin-embedded clinical specimens. This test is comprised of immunohistochemistry screening using a pan-receptor tyrosine kinase cocktail of antibodies to identify samples expressing TrkA (encoded by NTRK1), TrkB (encoded by NTRK2), TrkC (encoded by NTRK3), ROS1, and ALK followed by an RNA-based anchored multiplex polymerase chain reaction NGS assay...
March 29, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27016023/acute-mechanical-sensitization-of-peripheral-nociceptors-by-aldosterone-through-non-genomic-activation-of-membrane-bound-mineralocorticoid-receptors-in-naive-rats
#20
Mohammed Shaqura, Xiongjuan Li, Mohammed A Al-Madol, Sascha Tafelski, Antje Beyer-Koczorek, Shaaban A Mousa, Michael Schäfer
Recently, there is increasing interest in the role of peripheral mineralocorticoid receptors (MR) to modulate pain, but their localization in neurons and glia of the periphery and their distinct involvement in pain control remains elusive. In naive Wistar rats our double immunofluorescence confocal microscopy of the spinal cord, dorsal root ganglia, sciatic nerve and innervated skin revealed that MR predominantly colocalized with calcitonin-gene-related peptide (CGRP)- and trkA-immunoreactive (IR) nociceptive neurons and only marginally with myelinated trkB-IR mechanoreceptive and trkC-IR proprioreceptive neurons underscoring a pivotal role for MR in the modulation of pain...
August 2016: Neuropharmacology
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