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Tropomyosin

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https://www.readbyqxmd.com/read/28530094/troponin-c-mutations-partially-stabilize-the-active-state-of-regulated-actin-and-fully-stabilize-the-active-state-when-paired-with-%C3%AE-14-tnt
#1
Tamatha Baxley, Dylan Johnson, Jose Renato Pinto, Joseph Michael Chalovich
Striated muscle contraction is regulated by the actin associated proteins tropomyosin and troponin. Activation of myosin ATPase activity is lowest in the absence of both Ca2+ and activating crossbridges (i.e. S1-ADP or rigor S1). Binding of activating species of myosin to actin at saturating Ca2+ stabilizes the most active state (M state) of actin-tropomyosin-troponin (regulated actin). Ca2+ binding alone produces partial stabilization of the active state. The extent of stabilization at saturating Ca2+ depends on the isoform of the troponin subunits, the phosphorylation state of troponin and, in the case of cardiac muscle, the presence of hypertrophic cardiomyopathy producing mutants of troponin T and troponin I...
May 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28528122/probdnf-inhibits-proliferation-migration-and-differentiation-of-mouse-neural-stem-cells
#2
Jia-Yi Li, Jia Liu, Nimshitha Pavathuparambil Abdul Manaph, Larisa Bobrovskaya, Xin-Fu Zhou
ProBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is an important regulator of neurodegeneration, hippocampal long-term depression, and synaptic plasticity. ProBDNF and its receptors pan-neurotrophin receptor p75 (p75NTR), vps10p domain-containing receptor Sortilin and tropomyosin receptor kinase B (TrkB) are expressed in neuronal and glial cells. The role of proBDNF in regulation of neurogenesis is not fully defined. This study aims to uncover the function of proBDNF in regulating the differentiation, migration and proliferation of mouse neural stem cells (NSCs) in vitro...
May 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28524001/brain-derived-neurotrophic-factor-promotes-growth-of-neurons-and-neural-stem-cells-possibly-by-triggering-the-phosphoinositide-3-kinase-akt-glycogen-synthase-kinase-3%C3%AE-%C3%AE-catenin-pathway
#3
Jin-Wei Yang, Zhang Liang, Shi-Kang Deng Deng, Wei Ma, Xian-Bin Wang, Xing-Tong Li, Tong-Tong Wang, Yun-Fei Dai, Jian-Hui Guo, Li-Yan Li
BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a crucial role in promoting survival and differentiation of neurons and neural stem cells (NSCs), but the downstream regulating mechanisms remain poorly understood. OBJECTIVE: We investigated whether BDNF exerts its effect by triggering the phosphoinositide 3-kinase (PI3K), protein kinase B, PKB (AKT), glycogen synthase kinase-3β (GSK-3β) and β-catenin signaling pathway in cultured neurons and NSCs derived from the rat embryonic spinal cord...
May 18, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28522589/identification-of-cancer-targeted-tropomyosin-inhibitors-and-their-synergy-with-microtubule-drugs
#4
Mark A Currier, Justine R Stehn, Ashleigh Swain, Duo Chen, Jeff Hook, Eleanor Eiffe, Andrew Heaton, David Brown, Brooke Nartker, David W Eaves, Nina Kloss, Herbert Treutlein, Jun Zeng, Irina B Alieva, Vera B Dugina, Edna C Hardeman, Peter W Gunning, Timothy P Cripe
Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While anti-microtubule drugs are well-established, anti-actin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other anti-tropomyosin analogues for anti-cancer and on-target activity using a series of in vitro cell-based and biochemical assays...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28515680/trk-receptors-and-neurotrophin-cross-interactions-new-perspectives-toward-manipulating-therapeutic-side-effects
#5
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/28512288/lactic-acid-bacteria-specific-induction-of-cd4-foxp3-t-cells-ameliorates-shrimp-tropomyosin-induced-allergic-response-in-mice-via-suppression-of-mtor-signaling
#6
Linglin Fu, Jixiang Peng, Shushu Zhao, Yan Zhang, Xiurong Su, Yanbo Wang
The beneficial effects of probiotics have been described in allergic sensitization and diseases; however, many questions remain unanswered, such as characteristics of the most effective strains in modulation of allergic responses and how orally administered probiotics affect the systemic immune system. In the present work, oral administration of five lactic acid bacteria strains showed variable effects on protection against the allergic reaction in a mouse model of food allergy to shrimp tropomyosin (ST). The most effective anti-allergic strain, Bacillus coagulans 09...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498797/natb-mediated-protein-n-%C3%AE-terminal-acetylation-is-a-potential-therapeutic-target-in-hepatocellular-carcinoma
#7
Leire Neri, Marta Lasa, Alberto Elosegui-Artola, Delia D'Avola, Beatriz Carte, Cristina Gazquez, Sara Alve, Pere Roca-Cusachs, Mercedes Iñarrairaegui, Jose Herrero, J Prieto, Bruno Sangro, Rafael Aldabe
The identification of new targets for systemic therapy of hepatocellular carcinoma (HCC) is an urgent medical need. Recently, we showed that hNatB catalyzes the N-α-terminal acetylation of 15% of the human proteome and that this action is necessary for proper actin cytoskeleton structure and function. In tumors, cytoskeletal changes influence motility, invasion, survival, cell growth and tumor progression, making the cytoskeleton a very attractive antitumor target. Here, we show that hNatB subunits are upregulated in in over 59% HCC tumors compared to non-tumor tissue and that this upregulation is associated with microscopic vascular invasion...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28495385/derivatives-of-caffeic-acid-a-natural-antioxidant-as-the-basis-for-the-discovery-of-novel-nonpeptidic-neurotrophic-agents
#8
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/28494946/tropomodulins-and-leiomodins-actin-pointed-end-caps-and-nucleators-in-muscles
#9
REVIEW
Velia M Fowler, Roberto Dominguez
Cytoskeletal structures characterized by actin filaments with uniform lengths, including the thin filaments of striated muscles and the spectrin-based membrane skeleton, use barbed and pointed-end capping proteins to control subunit addition/dissociation at filament ends. While several proteins cap the barbed end, tropomodulins (Tmods), a family of four closely related isoforms in vertebrates, are the only proteins known to specifically cap the pointed end. Tmods are ∼350 amino acids in length, and comprise alternating tropomyosin- and actin-binding sites (TMBS1, ABS1, TMBS2, and ABS2)...
May 9, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28492466/ngf-and-its-receptors-in-the-regulation-of-inflammatory-response
#10
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/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
#11
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...
May 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28479141/neurodegenerative-effects-of-azithromycin-in-differentiated-pc12-cells
#12
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/28476569/design-and-synthesis-of-a-fluorinated-quinazoline-based-type-ii-trk-inhibitor-as-a-scaffold-for-pet-radiotracer-development
#13
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/28466254/celecoxib-alleviates-memory-deficits-by-downregulation-of-cox-2-expression-and-upregulation-of-the-bdnf-trkb-signaling-pathway-in-a-diabetic-rat-model
#14
Ying Yang, Ling Gao
Previous studies conveyed that diabetes causes learning and memory deficits. Data also suggest that celecoxib exerts an anti-hyperalgesic, anti-allodynic, and a plethora of other beneficial effects in diabetic rats. However, whether celecoxib could alleviate memory deficit in diabetic rat is unknown. In the present study, we aimed to examine the potential of celecoxib to counter memory deficits in diabetes. Experimental diabetes was induced by streptozotocin (STZ, 60 mg/kg) in male SD rats. Rats were divided into three groups (n = 16/group): normal control group injected with normal saline, diabetes group injected with STZ, and diabetes + celecoxib group in which diabetic rats were administered with celecoxib by gavage in drinking water (10 mg/kg) for 10 days in terms of which memory performance in animals was measured, hippocampal tissue harvested, and long-term potentiation assessed...
May 2, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28466092/repeated-social-defeat-and-the-rewarding-effects-of-cocaine-in-adult-and-adolescent-mice-dopamine-transcription-factors-probdnf-signaling-pathways-and-the-trkb-receptor-in-the-mesolimbic-system
#15
Sandra Montagud-Romero, Cristina Nuñez, M Carmen Blanco-Gandia, Elena Martínez-Laorden, María A Aguilar, Javier Navarro-Zaragoza, Pilar Almela, Maria-Victoria Milanés, María-Luisa Laorden, José Miñarro, Marta Rodríguez-Arias
RATIONALE: Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. OBJECTIVE: The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice...
May 2, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28465100/design-synthesis-and-sar-of-substituted-indoles-as-selective-trka-inhibitors
#16
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/28461162/bnn-20-a-synthetic-microneurotrophin-strongly-protects-dopaminergic-neurons-in-the-weaver-mouse-a-genetic-model-of-dopamine-denervation-acting-through-the-trkb-neurotrophin-receptor
#17
Konstantinos Botsakis, Theodora Mourtzi, Vasiliki Panagiotakopoulou, Malamati Vreka, Georgios T Stathopoulos, Iosif Pediaditakis, Ioannis Charalampopoulos, Achilleas Gravanis, Foteini Delis, Katerina Antoniou, Dimitrios Zisimopoulos, Christos D Georgiou, Nikolaos T Panagopoulos, Nikolaos Matsokis, Fevronia Angelatou
Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). However, in most cases, they cannot readily cross the human blood-brain-barrier (BBB). Herein, we propose as a therapeutic for PD the small molecule 17-beta-spiro-[5-androsten-17,2'-oxiran]-3beta-ol (BNN-20), a synthetic analogue of DHEA, which crosses the BBB and is deprived of endocrine side-effects. Using the "weaver" mouse, a genetic model of PD, which exhibits progressive dopaminergic neurodegeneration in the Substantia Nigra (SN), we have shown that long-term administration (P1-P21) of BNN-20 almost fully protected the dopaminergic neurons and their terminals, via i) a strong anti-apoptotic effect, probably mediated through the Tropomyosin receptor kinase B (TrkB) neurotrophin receptor's PI3K-Akt-NF-κB signaling pathway, ii) by exerting an efficient antioxidant effect, iii) by inducing significant anti-inflammatory activity and iv) by restoring Brain-Derived Neurotrophic Factor (BDNF) levels...
April 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28451885/impact-of-high-fat-diet-and-early-stress-on-depressive-like-behavior-and-hippocampal-plasticity-in-adult-male-rats
#18
Danusa Mar Arcego, Ana Paula Toniazzo, Rachel Krolow, Carine Lampert, Carolina Berlitz, Emily Dos Santos Garcia, Fabrício do Couto Nicola, Juliana Bender Hoppe, Mariana Maier Gaelzer, Caroline Peres Klein, Camilla Lazzaretti, Carla Dalmaz
During development, the brain goes through fundamental processes, including organization of neural networks and plasticity. Environmental interventions may change initial brain programming, leading to long-lasting effects and altering the susceptibility to psychopathologies, including depression disorder. It is known that depression is a psychiatric disorder with a high prevalence worldwide, including high rates among adolescents. In this study, we evaluated whether social isolation in the prepubertal period and chronic use of high-fat diet (HFD) may induce depressive-like behavior in male adult rats...
April 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28450301/neuron-specific-caveolin-1-overexpression-improves-motor-function-and-preserves-memory-in-mice-subjected-to-brain-trauma
#19
Junji Egawa, Jan M Schilling, Weihua Cui, Edmund Posadas, Atsushi Sawada, Basheer Alas, Alice E Zemljic-Harpf, McKenzie J Fannon-Pavlich, Chitra D Mandyam, David M Roth, Hemal H Patel, Piyush M Patel, Brian P Head
Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes...
April 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28449083/proteomic-response-to-linoleic-acid-hydroperoxide-in-saccharomyces-cerevisiae
#20
Patrick J O'Doherty, Alamgir Khan, Adam J Johnson, Peter J Rogers, Trevor D Bailey, Ming J Wu
Yeast AP-1 transcription factor (Yap1p) and the enigmatic oxidoreductases Oye2p and Oye3p are involved in counteracting lipid oxidants and their unsaturated breakdown products. In order to uncover the response to linoleic acid hydroperoxide (LoaOOH) and the roles of Oye2p, Oye3p, and Yap1p, we carried out proteomic analysis of the homozygous deletion mutants oye3Δ, oye2Δ, and yap1Δ alongside the diploid parent strain BY4743. The findings demonstrate that deletion of YAP1 narrowed the response to LoaOOH, as the number of proteins differentially expressed in yap1Δ was 70% of that observed in BY4743...
April 25, 2017: FEMS Yeast Research
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