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https://www.readbyqxmd.com/read/29222769/neurotrophic-factors-an-overview
#1
Stephen D Skaper
The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons and have since been shown to control a number of aspects of survival, development, and function of neurons in both the central and peripheral nervous systems. Limiting quantities of neurotrophins during development control the numbers of surviving neurons to ensure a match between neurons and the requirement for a suitable density of target innervation. Biological effects of each of the four mammalian neurotrophins are mediated through activation of one or more of the three members of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases (TrkA, TrkB, and TrkC)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29208634/the-synthetic-microneurotrophin-bnn27-affects-retinal-function-in-streptozotocin-induced-diabetic-rats
#2
Ruth Ibán-Arias, Silvia Lisa, Niki Mastrodimou, Despina Kokona, Emmanuil Koulakis, Panagiota Iordanidou, Antonis Kouvarakis, Myrto Fothiadaki, Sofia Papadogkonaki, Aggeliki Sotiriou, Haralambos E Katerinopoulos, Achille Gravanis, Ioannis Charalampopoulos, Kyriaki Thermos
BNN27, a C17-spiroepoxy derivative of DHEA, was shown to have anti-apoptotic properties via mechanisms involving the NGF receptors (TrkA/ p75NTR). In this study we examined the effects of BNN27 on neural/glial cell function, apoptosis and inflammation in the experimental rat streptozotocin (STZ)-model of diabetic retinopathy (DR). The ability of BNN27 to activate the TrkA receptor and regulate p75NTR expression was investigated. BNN27 (2,10,50mg/kg,7days,i.p.) administration four weeks post STZ-injection (Paradigm A) reversed the diabetes-induced glial activation, loss of function of amacrine cells (bNOS/TH expression) and ganglion cell axons via a TrkAR-dependent mechanism...
December 5, 2017: Diabetes
https://www.readbyqxmd.com/read/29200998/attenuation-of-the-infiltration-of-angiotensin-ii-expressing-cd3-t-cells-and-the-modulation-of-nerve-growth-factor-in-lumbar-dorsal-root-ganglia-a-possible-mechanism-underpinning-analgesia-produced-by-ema300-an-angiotensin-ii-type-2-at2-receptor-antagonist
#3
Nemat Khan, Arjun Muralidharan, Maree T Smith
Recent preclinical and proof-of-concept clinical studies have shown promising analgesic efficacy of selective small molecule angiotensin II type 2 (AT2) receptor antagonists in the alleviation of peripheral neuropathic pain. However, their cellular and molecular mechanism of action requires further investigation. To address this issue, groups of adult male Sprague-Dawley rats with fully developed unilateral hindpaw hypersensitivity, following chronic constriction injury (CCI) of the sciatic nerve, received a single intraperitoneal bolus dose of the small molecule AT2 receptor antagonist, EMA300 (10 mg kg-1), or vehicle...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29196027/cancer-chemotherapy-in-early-life-significantly-alters-the-maturation-of-pain-processing
#4
G J Hathway, Emily Murphy, Joseph Lloyd, Charles Greenspon, R P Hulse
Advances in paediatric cancer treatment have led to a ten year survival rate greater than 75%. Platinum-based chemotherapies (e.g.cisplatin) induce peripheral sensory neuropathy in adult and paedriatric cancer patients. The period from birth through to adulthood represents a period of maturation within nociceptive systems. Here we investigated how cisplatin impacts upon postnatal maturation of nociceptive systems. Neonatal Wistar rats (Postnatal day (P) 7) were injected (i.p.) daily with either vehicle (PBS) or cisplatin (1mg/kg) for five consecutive days...
November 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/29175861/ngf-reprograms-metastatic-melanoma-to-a-bipotent-glial-melanocyte-neural-crest-like-precursor
#5
Jennifer C Kasemeier-Kulesa, Morgan H Romine, Jason A Morrison, Caleb M Bailey, Danny R Welch, Paul M Kulesa
Melanoma pathogenesis from normal neural crest-derived melanocytes is often fatal due to aggressive cell invasion throughout the body. The identification of signals that reprogram de-differentiated, metastatic melanoma cells to a less aggressive and stable phenotype would provide a novel strategy to limit disease progression. In this study, we identify and test the function of developmental signals within the chick embryonic neural crest microenvironment to reprogram and sustain the transition of human metastatic melanoma to a neural crest cell-like phenotype...
November 24, 2017: Biology Open
https://www.readbyqxmd.com/read/29172008/effects-of-cerebrolysin-on-nerve-growth-factor-system-in-the-aging-rat-brain
#6
Mikhail Stepanichev, Mikhail Onufriev, Viktor Aniol, Sofia Freiman, Hemma Brandstaetter, Stefan Winter, Natalia Lazareva, Alla Guekht, Natalia Gulyaeva
BACKGROUND: Aging is associated with some cognitive decline and enhanced risk of development of neurodegenerative diseases. It is assumed that altered metabolism and functions of neurotrophin systems may underlie these age-related functional and structural modifications. CerebrolysinTM (CBL) is a neuropeptide mixture with neurotrophic effects, which is widely used for the treatment of stroke and traumatic brain injury patients. It is also evident that CBL has an overall beneficial effect and a favorable benefit-risk ratio in patients with dementia...
2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/29166838/-express-immunohistochemical-localization-of-ngf-trka-and-p75-in-the-bone-and-articular-cartilage-of-the-mouse-femur
#7
Stephane R Chartier, Stefanie A Mitchell, Lisa A Majuta, Patrick Mantyth
No abstract text is available yet for this article.
January 1, 2017: Molecular Pain
https://www.readbyqxmd.com/read/29165617/selective-activation-of-striatal-ngf-trka-p75ntr-mapk-intracellular-signaling-in-rats-that-show-suppression-of-methamphetamine-intake-30-days-following-drug-abstinence
#8
Oscar V Torres, Subramanian Jayanthi, Michael T McCoy, Jean Lud Cadet
Background: The continuing epidemic of methamphetamine (METH) addiction has prompted research aimed at understanding striatal dysfunctions potentially associated with long-term METH use. Methods: Here, we investigated transcriptional and translational alterations in the expression of neurotrophic factors in the rat striatum at 30 days following METH SA and footshock punishment. Male Sprague-Dawley rats were trained to self-administer METH (0.1 mg/kg/injection, i...
November 20, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29163051/young-human-cholinergic-neurons-respond-to-physiological-regulators-and-improve-cognitive-symptoms-in-an-animal-model-of-alzheimer-s-disease
#9
Annamaria Morelli, Erica Sarchielli, Giulia Guarnieri, Elisabetta Coppi, Daniela Pantano, Paolo Comeglio, Pamela Nardiello, Anna M Pugliese, Lara Ballerini, Rosanna Matucci, Stefano Ambrosini, Giuseppe Castronovo, Rosa Valente, Benedetta Mazzanti, Sandra Bucciantini, Mario Maggi, Fiorella Casamenti, Pasquale Gallina, Gabriella B Vannelli
The degeneration of cholinergic neurons of the nucleus basalis of Meynert (NBM) in the basal forebrain (BF) is associated to the cognitive decline of Alzheimer's disease (AD) patients. To date no resolutive therapies exist. Cell-based replacement therapy is a strategy currently under consideration, although the mechanisms underlying the generation of stem cell-derived NBM cholinergic neurons able of functional integration remain to be clarified. Since fetal brain is an optimal source of neuronal cells committed towards a specific phenotype, this study is aimed at isolating cholinergic neurons from the human fetal NBM (hfNBMs) in order to study their phenotypic, maturational and functional properties...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29137974/effects-and-mechanisms-of-matrix-metalloproteinase2-on-neural-differentiation-of-induced-pluripotent-stem-cells
#10
Tao Shu, Chang Liu, Mao Pang, Juan Wang, Bin Liu, Wei Zhou, Xuan Wang, Tao Wu, Qiyou Wang, Limin Rong
Induced pluripotent stem cells (iPSCs) possess the potential to differentiate into neural lineage cells. Matrix metalloproteinase 2 (MMP2), an endopeptidase in the extracellular matrix, has been shown to protect neural cells from injury. However, the mechanisms and effects of MMP2 on neural differentiation of iPSCs remain poorly understood. Here, we demonstrated a role for MMP2 in the differentiation of iPSCs to neurons via the AKT pathway. Treatment of iPSCs with MMP2 promoted their proliferation and differentiation into neural stem cells (NSCs), and then into neurons...
November 11, 2017: Brain Research
https://www.readbyqxmd.com/read/29126931/phytochemical-allylguaiacol-exerts-a-neuroprotective-effect-on-hippocampal-cells-and-ameliorates-scopolamine-induced-memory-impairment-in-mice
#11
Hye-Sun Lim, Bu-Yeo Kim, Yu Jin Kim, Soo-Jin Jeong
Allylguaiacol is a phytochemical occurring in various plants such as cloves, cinnamon, basil, and nutmeg. Pharmacological effects of allylguaiacol include antimicrobial, anti-inflammatory, anticancer, antioxidant, and neuroprotective activity. Although allylguaiacol is considered to have neuroprotective effects, there is no report on its regulatory mechanisms at the molecular level. In the present study, we investigated the mechanisms of allylguaiacol as an antioxidant and neuroprotective agent using hydrogen peroxide (H2O2)-treated HT22 hippocampal cells...
November 7, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29118225/activity-of-entrectinib-in-a-patient-with-the-first-reported-ntrk-fusion-in-neuroendocrine-cancer
#12
Darren Sigal, Marie Tartar, Marin Xavier, Fei Bao, Patrick Foley, David Luo, Jason Christiansen, Zachary Hornby, Edna Chow Maneval, Pratik Multani
Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including NTRK1, 2, and 3, encode the proteins TRKA, TRKB, TRKC, respectively, involved in normal nerve development. Because NETs develop from the diffuse neuroendocrine system, we sought to determine whether NTRK alterations occur in NETs and whether TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely of the small intestine, was enrolled on the STARTRK2 trial (ClinicalTrials...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29117739/cardiac-autonomic-denervation-and-expression-of-neurotrophins-ngf-and-bdnf-and-their-receptors-during-experimental-chagas-disease
#13
Natália Katley Oliveira, Rodrigo Novaes Ferreira, Sara Delaine Nogueira Lopes, Egler Chiari, Elizabeth Ribeiro da Silva Camargos, Patricia Massara Martinelli
Although cardiac dysautonomia is a distinctive feature of Chagas disease, its clinical and functional significance is still being speculated. Neurotrophic factors are potentially involved; however, studies of their effect in this infection are rare. Ultrastructural abnormalities in autonomic varicosities, levels of both nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF), as well as the expression of their receptors, were analysed in the heart of a rat model of Trypanosoma infection. Predominantly, at the early stage of the infection, cardiac autonomic varicosities displayed several signs of degeneration parallel to the elevation of cardiac levels of NGF, as well as expression of the receptors TrkA and p75NTR...
November 8, 2017: Growth Factors
https://www.readbyqxmd.com/read/29108999/generation-of-rationally-designed-nerve-growth-factor-ngf-variants-with-receptor-specificity
#14
Laura A Carleton, Reka Chakravarthy, Almer M van der Sloot, Katarzyna Mnich, Luis Serrano, Afshin Samali, Adrienne M Gorman
Nerve growth factor (NGF) is the prototypic member of the neurotrophin family and binds two receptors, TrkA and the 75 kDa neurotrophin receptor (p75(NTR)), through which diverse and sometimes opposing effects are mediated. Using the FoldX protein design algorithm, we generated eight NGF variants with different point mutations predicted to have altered binding to TrkA or p75(NTR). Of these, the I31R NGF variant exhibited specific binding to p75(NTR). The generation of this NGF variant with selective affinity for p75(NTR) can be used to enhance understanding of neurotrophin receptor imbalance in diseases and identifies a key targetable residue for the development of small molecules to disrupt binding of NGF to TrkA with potential uses in chronic pain...
November 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29106982/distinct-trka-and-ret-modulated-negative-and-positive-neuropathic-behaviors-in-a-mouse-model-of-resiniferatoxin-induced-small-fiber-neuropathy
#15
Yu-Lin Hsieh, Hung-Wei Kan, Hao Chiang, Yi-Chen Lee, Sung-Tsang Hsieh
Neurotrophic factors and their corresponding receptors play key roles in the maintenance of different phenotypic dorsal root ganglion (DRG) neurons, the axons of which degenerate in small fiber neuropathy, leading to various neuropathic manifestations. Mechanisms underlying positive and negative symptoms of small fiber neuropathy have not been systematically explored. This study investigated the molecular basis of these seemingly paradoxical neuropathic behaviors according to the profiles of TrkA and Ret with immunohistochemical and pharmacological interventions in a mouse model of resiniferatoxin (RTX)-induced small fiber neuropathy...
October 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29102663/signaling-pathways-relevant-to-nerve-growth-factor-induced-upregulation-of-transient-receptor-potential-m8-expression
#16
Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Jin Nakahara, Toshihiko Shimizu, Haruki Toriumi, Michisuke Yuzaki, Norihiro Suzuki
Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that primarily detects the innocuous cold. In pathological conditions, TRPM8 plays a role in the development of cold hyperalgesia/allodynia. Nerve growth factor (NGF) is an important mediator involved in various pain disorders. In the present study, the NGF-TrkA pathway increased TRPM8 expression by stabilizing TRPM8 mRNA through the actions of phosphatidylinositol 3-kinase and p38 MAP kinase. Moreover, c-Jun N-terminal kinase and Src tyrosine kinase were identified as a positive and negative regulator of TRPM8 expression, respectively, via post-transcriptional mechanisms independent of mRNA stabilization...
November 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/29083050/alternating-r-chop-and-r-cytarabine-is-a-safe-and-effective-regimen-for-transplant-ineligible-patients-with-a-newly-diagnosed-mantle-cell-lymphoma
#17
Pavel Klener, Eva Fronkova, David Belada, Kristina Forsterova, Robert Pytlik, Marketa Kalinova, Martin Simkovic, David Salek, Heidi Mocikova, Vit Prochazka, Petra Blahovcova, Andrea Janikova, Jana Markova, Ales Obr, Adela Berkova, Jozef Kubinyi, Martina Vaskova, Ester Mejstrikova, Vit Campr, Radek Jaksa, Roman Kodet, Kyra Michalova, Jan Trka, Marek Trneny
Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first-line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3 + 3 cycles of R-CHOP and R-cytarabine for newly diagnosed transplant-ineligible MCL patients. A total of 73 patients were enrolled with median age 70 years...
October 30, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/29075557/rats-bred-for-low-and-high-running-capacity-display-alterations-in-peripheral-tissues-and-nerves-relevant-to-neuropathy-and-pain
#18
Michael A Cooper, Megan M Jack, Janelle M Ryals, Page Hayley, Taylor Escher, Lauren G Koch, Steven L Britton, Shelby M Raupp, Michelle K Winter, Kenneth E McCarson, Paige C Geiger, John P Thyfault, Douglas E Wright
INTRODUCTION: Diet and activity are recognized as modulators of nervous system disease, including pain. Studies of exercise consistently reveal a benefit on pain. This study focused on female rats to understand differences related to metabolic status and peripheral nerve function in females. METHODS: Here, we investigated parameters of peripheral nerve function relevant to pain in rats selectively bred for high (high-capacity runners; HCR) or low endurance exercise capacity (low-capacity runners; LCR) resulting in divergent intrinsic aerobic capacities and susceptibility for metabolic conditions...
October 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29051534/surface-marker-profiling-of-sh-sy5y-cells-enables-small-molecule-screens-identifying-bmp4-as-a-modulator-of-neuroblastoma-differentiation
#19
Fraua Christina Ferlemann, Vishal Menon, Alexandra Larisa Condurat, Jochen Rößler, Jan Pruszak
Neuroblastoma is the most common extra-cranial solid tumor in children. Its broad spectrum of clinical outcomes reflects the underlying inherent cellular heterogeneity. As current treatments often do not lead to tumor eradication, there is a need to better define therapy-resistant neuroblastoma and to identify new modulatory molecules. To this end, we performed the first comprehensive flow cytometric characterization of surface molecule expression in neuroblastoma cell lines. Exploiting an established clustering algorithm (SPADE) for unbiased visualization of cellular subsets, we conducted a multiwell screen for small molecule modulators of neuroblastoma phenotype...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29037860/neurotrophin-receptors-trka-p75-ntr-and-sortilin-are-increased-and-targetable-in-thyroid-cancer
#20
Sam Faulkner, Philip Jobling, Christopher Rowe, Sonia Rodriguez-Oliveira, Severine Roselli, Rick Thorne, Christopher Oldmeadow, John Attia, Chen Chen Jiang, Xu Dong Zhang, Marjorie M Walker, Hubert Hondermarck
Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75(NTR), and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0...
October 14, 2017: American Journal of Pathology
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