Purinergic Signalling in Neurodegeneration, Neuroprotection and Neuroregeneration
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Applying Screening Techniques to Two Orphan Gpcrs
Universidade de Lisboa Faculdade de Farmácia Deorphanization of receptors: Applying screening techniques to two orphan GPCRs Ana Catarina Rufas da Silva Santos Mestrado Integrado em Ciências Farmacêuticas 2019 Universidade de Lisboa Faculdade de Farmácia Deorphanization of receptors: Applying screening techniques to two orphan GPCRs Ana Catarina Rufas da Silva Santos Monografia de Mestrado Integrado em Ciências Farmacêuticas apresentada à Universidade de Lisboa através da Faculdade de Farmácia Orientadora: Ghazl Al Hamwi, PhD Student Co-Orientadora: Professora Doutora Elsa Maria Ribeiro dos Santos Anes, Professora Associada com Agregação em Microbiologia 2019 Abstract G-Protein Coupled Receptors represent one of the largest families of cellular receptors discovered and one of the main sources of attractive drug targets. In contrast, it also has a large number of understudied or orphan receptors. Pharmacological assays such as β-Arrestin recruitment assays, are one of the possible approaches for deorphanization of receptors. In this work, I applied the assay system previously mentioned to screen compounds in two orphan receptors, GRP37 and MRGPRX3. GPR37 has been primarily associated with a form of early onset Parkinsonism due to its’ expression patterns, and physiological role as substrate to ubiquitin E3, parkin. Although extensive literature regarding this receptor is available, the identification of a universally recognized ligand has not yet been possible. Two compounds were proposed as ligands, but both were met with controversy. These receptor association with Autosomal Recessive Juvenile Parkinson positions it as a very attractive drug target, and as such its’ deorphanization is a prime objective for investigators in this area. Regarding MRGPRX3 information is much scarcer. -
Protective Effects of Anthocyanins on the Ectonucleotidase Activity in the Impairment of Memory Induced by Scopolamine in Adult Rats
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Life Sciences 91 (2012) 1221–1228 Contents lists available at SciVerse ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Protective effects of anthocyanins on the ectonucleotidase activity in the impairment of memory induced by scopolamine in adult rats Jessié M. Gutierres a,⁎, Fabiano B. Carvalho a, Maria R.C. Schetinger a, Marília V. Rodrigues a, Roberta Schmatz a, Victor C. Pimentel a, Juliano M. Vieira a, Michele M. Rosa a, Patrícia Marisco a, Daniela A. Ribeiro a, Claudio Leal a, Maribel A. Rubin a, Cinthia M. Mazzanti c, Roselia Spanevello b,⁎⁎ a Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil b Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário-Capão do Leão 96010-900 Pelotas, RS, Brazil c Clínica de Pequenos animais, Centro de Ciências Rurais, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil article info abstract Article history: Aims: We investigated whether the treatment with anthocyanins prevents the scopolamine-induced memory Received 24 March 2012 deficits and whether ectonucleotidase activities and purine levels are altered in the cerebral cortex (CC) and Accepted 19 September 2012 hippocampus (HC) in this model of mnemonic deficit in rats. Main methods: The animals were divided into 4 experimental groups: control (vehicle), anthocyanins (Antho), Keywords: scopolamine (SCO), and scopolamine plus anthocyanins (SCO+Antho). After seven days of treatment, they Anthocyanins were tested in the inhibitory avoidance task and open field test and submitted to euthanasia. -
Preladenant | Medchemexpress
Inhibitors Product Data Sheet Preladenant • Agonists Cat. No.: HY-10889 CAS No.: 377727-87-2 Molecular Formula: C₂₅H₂₉N₉O₃ • Molecular Weight: 503.56 Screening Libraries Target: Adenosine Receptor Pathway: GPCR/G Protein Storage: Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month SOLVENT & SOLUBILITY In Vitro DMSO : 5 mg/mL (9.93 mM; Need ultrasonic) Mass Solvent 1 mg 5 mg 10 mg Concentration Preparing 1 mM 1.9859 mL 9.9293 mL 19.8586 mL Stock Solutions 5 mM 0.3972 mL 1.9859 mL 3.9717 mL 10 mM --- --- --- Please refer to the solubility information to select the appropriate solvent. In Vivo 1. Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline Solubility: 0.5 mg/mL (0.99 mM); Suspended solution; Need ultrasonic 2. Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline) Solubility: 0.5 mg/mL (0.99 mM); Suspended solution; Need ultrasonic 3. Add each solvent one by one: 10% DMSO >> 90% corn oil Solubility: ≥ 0.5 mg/mL (0.99 mM); Clear solution BIOLOGICAL ACTIVITY Description Preladenant is a potent and competitive antagonist of the human adenosine A2A receptor with a Ki of 1.1 nM and has over 1000-fold selectivity over other adenosine receptors. [1] IC₅₀ & Target Ki: 1.1 nM (Adenosine A2A receptor) In Vitro Preladenant also completely antagonizes cAMP in cells expressing the recombinant human A2A receptor. Preladenant is determined to has KB values of 1.3 nM at the A2A receptor; the value is in good agreement with the Ki value determined in Page 1 of 3 www.MedChemExpress.com the radioligand binding assay. -
Purinergic Signalling in Skin
PURINERGIC SIGNALLING IN SKIN AINA VH GREIG MA FRCS Autonomic Neuroscience Institute Royal Free and University College School of Medicine Rowland Hill Street Hampstead London NW3 2PF in the Department of Anatomy and Developmental Biology University College London Gower Street London WCIE 6BT 2002 Thesis Submitted for the Degree of Doctor of Philosophy University of London ProQuest Number: U643205 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U643205 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT Purinergic receptors, which bind ATP, are expressed on human cutaneous kératinocytes. Previous work in rat epidermis suggested functional roles of purinergic receptors in the regulation of proliferation, differentiation and apoptosis, for example P2X5 receptors were expressed on kératinocytes undergoing proliferation and differentiation, while P2X? receptors were associated with apoptosis. In this thesis, the aim was to investigate the expression of purinergic receptors in human normal and pathological skin, where the balance between these processes is changed. A study was made of the expression of purinergic receptor subtypes in human adult and fetal skin. -
1.Intro Corregida
Heterómeros de receptores de dopamina como dianas terapéuticas en la enfermedad de Parkinson y en discinesias inducidas por el tratamiento con L-DOPA Daniel Farré Pérez ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tdx.cat) i a través del Dipòsit Digital de la UB (diposit.ub.edu) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA. La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR (www.tdx.cat) y a través del Repositorio Digital de la UB (diposit.ub.edu) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB. -
P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases
International Journal of Molecular Sciences Review P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases Derek Strassheim 1, Alexander Verin 2, Robert Batori 2 , Hala Nijmeh 3, Nana Burns 1, Anita Kovacs-Kasa 2, Nagavedi S. Umapathy 4, Janavi Kotamarthi 5, Yash S. Gokhale 5, Vijaya Karoor 1, Kurt R. Stenmark 1,3 and Evgenia Gerasimovskaya 1,3,* 1 The Department of Medicine Cardiovascular and Pulmonary Research Laboratory, University of Colorado Denver, Aurora, CO 80045, USA; [email protected] (D.S.); [email protected] (N.B.); [email protected] (V.K.); [email protected] (K.R.S.) 2 Vascular Biology Center, Augusta University, Augusta, GA 30912, USA; [email protected] (A.V.); [email protected] (R.B.); [email protected] (A.K.-K.) 3 The Department of Pediatrics, Division of Critical Care Medicine, University of Colorado Denver, Aurora, CO 80045, USA; [email protected] 4 Center for Blood Disorders, Augusta University, Augusta, GA 30912, USA; [email protected] 5 The Department of BioMedical Engineering, University of Wisconsin, Madison, WI 53706, USA; [email protected] (J.K.); [email protected] (Y.S.G.) * Correspondence: [email protected]; Tel.: +1-303-724-5614 Received: 25 August 2020; Accepted: 15 September 2020; Published: 18 September 2020 Abstract: Purinergic G-protein-coupled receptors are ancient and the most abundant group of G-protein-coupled receptors (GPCRs). The wide distribution of purinergic receptors in the cardiovascular system, together with the expression of multiple receptor subtypes in endothelial cells (ECs) and other vascular cells demonstrates the physiological importance of the purinergic signaling system in the regulation of the cardiovascular system. -
The Two Tondition to Martin
THETWO TONDITIONUS 20170306038A1 TO MARTIN ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017/ 0306038 A1 BROGDON et al. (43 ) Pub . Date : Oct. 26 , 2017 ( 54 ) COMPOSITIONS AND METHODS OF USE Publication Classification FOR AUGMENTED IMMUNE RESPONSE (51 ) Int. Cl. AND CANCER THERAPY CO7K 16 / 28 ( 2006 .01 ) (71 ) Applicants : Jennifer BROGDON , Sudbury , MA CO7K 16 / 28 ( 2006 . 01) (US ) ; Daniela CIPOLLETTA , A61K 45 / 06 (2006 . 01 ) Arlington , MA (US ) ; Glenn A61K 39 /00 ( 2006 .01 ) DRANOFF , Lexington , MA ( US ) ; A61K 39 /00 (2006 .01 ) Deborah A . KNEE . Del Mar. CA (US ): (52 ) U . S . Cl. CPC . .. .. CO7K 16 / 2878 ( 2013. 01 ) ; C07K 16 /2818 Fei WANG , San Diego , CA (US ) ( 2013 .01 ) ; A61K 45 / 06 ( 2013 .01 ) ; CO7K ( 72 ) Inventors : Jennifer BROGDON , Sudbury , MA 2317 / 74 ( 2013 . 01 ) ; C07K 2317 / 732 ( 2013 .01 ) ; (US ) ; Daniela CIPOLLETTA , CO7K 2317 / 567 ( 2013 . 01 ) ; COZK 2317 / 56 Arlington , MA (US ) ; Glenn ( 2013 .01 ) ; CO7K 2317 /51 ( 2013 .01 ) ; CO7K DRANOFF , Lexington , MA (US ) ; 2317 / 24 (2013 .01 ) ; A61K 2039 /507 (2013 . 01 ) ; Deborah A . KNEE , Del Mar, CA (US ) ; A61K 2039 /505 ( 2013 . 01 ) ; COZK 2317 / 75 ( 2013 . 01 ) ; CO7K 2317/ 92 ( 2013 .01 ) ; CO7K Fei WANG , San Diego , CA (US ) 2317/ 515 (2013 . 01) ( 21 ) Appl. No. : 15 /517 ,872 (57 ) ABSTRACT (22 ) PCT Filed : Oct . 8 , 2015 The present invention provides antibody compositions , (86 ) PCT No. : PCT/ US2015 / 054770 including , e . g ., antibodies, engineered antibodies and anti body fragments that bind to a tumor necrosis factor receptor $ 371 ( c ) ( 1 ), superfamily member ( i. e . , 18 ) , and compositions comprising ( 2 ) Date : Apr. -
Hypoxia Modulates Platelet Purinergic Signalling Pathways
Published online: 2019-12-13 THIEME Cellular Haemostasis and Platelets 253 Hypoxia Modulates Platelet Purinergic Signalling Pathways Gordon G. Paterson1,2 Jason M. Young1,2 Joseph A. Willson3 Christopher J. Graham1,2 Rebecca C. Dru1,2 Eleanor W. Lee1,2 Greig S. Torpey1,2 Sarah R. Walmsley3 Melissa V. Chan4 Timothy D. Warner4 John Kenneth Baillie1,5,6 Alfred Arthur Roger Thompson1,7 1 APEX (Altitude Physiology Expeditions), Edinburgh, United Kingdom Address for correspondence Alfred Arthur Roger Thompson, BSc, MB 2 Edinburgh Medical School, University of Edinburgh, Edinburgh, ChB,MRCP,PhD,DepartmentofInfection,Immunityand United Kingdom Cardiovascular Disease, University of Sheffield, M127a, Royal 3 University of Edinburgh Centre for Inflammation Research, The Hallamshire Hospital, Beech Hill Road, Sheffield S10 2RX, Queen’s Medical Research Institute, University of Edinburgh, United Kingdom (e-mail: R.Thompson@sheffield.ac.uk). Edinburgh, United Kingdom 4 Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom 5 Division of Genetics and Genomics, The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom 6 Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United Kingdom 7 Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom Thromb Haemost 2020;120:253–261. Abstract Background Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. -
Alzheimer and Purinergic Signaling: Just a Matter of Inflammation?
cells Review Alzheimer and Purinergic Signaling: Just a Matter of Inflammation? Stefania Merighi 1, Tino Emanuele Poloni 2, Anna Terrazzan 1, Eva Moretti 1, Stefania Gessi 1,* and Davide Ferrari 3,* 1 Department of Translational Medicine and for Romagna, University of Ferrara, 44100 Ferrara, Italy; [email protected] (S.M.); [email protected] (A.T.); [email protected] (E.M.) 2 Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, 20081 Milan, Italy; [email protected] 3 Department of Life Science and Biotechnology, University of Ferrara, 44100 Ferrara, Italy * Correspondence: [email protected] (S.G.); [email protected] (D.F.) Abstract: Alzheimer’s disease (AD) is a widespread neurodegenerative pathology responsible for about 70% of all cases of dementia. Adenosine is an endogenous nucleoside that affects neurode- generation by activating four membrane G protein-coupled receptor subtypes, namely P1 receptors. One of them, the A2A subtype, is particularly expressed in the brain at the striatal and hippocampal levels and appears as the most promising target to counteract neurological damage and adenosine- dependent neuroinflammation. Extracellular nucleotides (ATP, ADP, UTP, UDP, etc.) are also released from the cell or are synthesized extracellularly. They activate P2X and P2Y membrane receptors, eliciting a variety of physiological but also pathological responses. Among the latter, the chronic inflammation underlying AD is mainly caused by the P2X7 receptor subtype. In this review we offer an overview of the scientific evidence linking P1 and P2 mediated purinergic signaling to AD devel- opment. We will also discuss potential strategies to exploit this knowledge for drug development. -
Ectonucleotidase Expression on Human Amnion Epithelial Cells
Ectonucleotidase Expression on Human Amnion Epithelial Cells: Adenosinergic Pathways and Dichotomic Effects on Immune Effector Cell Populations This information is current as of September 28, 2021. Fabio Morandi, Alberto L. Horenstein, Valeria Quarona, Angelo Corso Faini, Barbara Castella, Raghuraman C. Srinivasan, Stephen C. Strom, Fabio Malavasi and Roberto Gramignoli J Immunol published online 26 December 2018 Downloaded from http://www.jimmunol.org/content/early/2018/12/23/jimmun ol.1800432 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2018/12/23/jimmunol.180043 Material 2.DCSupplemental Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2018 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published December 26, 2018, doi:10.4049/jimmunol.1800432 The Journal of Immunology Ectonucleotidase Expression on Human Amnion Epithelial Cells: Adenosinergic Pathways and Dichotomic Effects on Immune Effector Cell Populations Fabio Morandi,*,1 Alberto L. Horenstein,†,‡,x,1 Valeria Quarona,† Angelo Corso Faini,† Barbara Castella,† Raghuraman C. -
(12) United States Patent (10) Patent No.: US 9.402,830 B2 Cialella Et Al
USOO940283OB2 (12) United States Patent (10) Patent No.: US 9.402,830 B2 Cialella et al. (45) Date of Patent: * Aug. 2, 2016 (54) METHODS OF TREATING DYSKINESIA AND FOREIGN PATENT DOCUMENTS RELATED DSORDERS WO 93.18767 A1 9, 1993 (71) Applicant: Melior Discovery, Inc., Exton, PA (US) OTHER PUBLICATIONS (72) Inventors: John Ciallella, Exton, PA (US); John Afanasev et al., Effects of amphetamine and Sydnocarbon dopamine Gruner, Exton, PA (US); Andrew G. release and free radical generation in rat striatum, Pharmacol Reaume, Exton, PA (US); Michael S. Biochem Behav, 2001, 69(3-4):653-8. Saporito, Exton, PA (US) Anderzhanova et al., Effect of d-amphetamine and Sydnocarb on the extracellular level of dopamine, 3,4-dihydroxyphenylacetic acid, and (73) Assignee: Melior Discovery, Inc., Exton, PA (US) hydroxyl radicals generation in rat striatum, Ann NY AcadSci, 2000, 914:137-45. Anderzhanova et al., Effects of Sydnocarb and D-amphetamine on the (*) Notice: Subject to any disclaimer, the term of this extracellular levels of amino acids in the rat caudate-putamen, Eur J patent is extended or adjusted under 35 Pharmacol, 2001, 428(1):87-95. U.S.C. 154(b) by 0 days. Bashkatova et al., Neuroshemical changes and neurotoxic effects of This patent is Subject to a terminal dis an acute treatment with Sydnocarb, a novel psychostimulant: com claimer. parison with D-amphetamine, Ann NY AcadSci, 2002,965: 180-192. Cody, Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results, J Occup Environ Med, (21) Appl. No.: 14/702,242 2002, 44(5):435-50. -
Characterization of the Contractile P2Y14 Receptor in Mouse Coronary and Cerebral Arteries ⇑ Kristian Agmund Haanes , Lars Edvinsson
FEBS Letters 588 (2014) 2936–2943 journal homepage: www.FEBSLetters.org Characterization of the contractile P2Y14 receptor in mouse coronary and cerebral arteries ⇑ Kristian Agmund Haanes , Lars Edvinsson Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Nordre Ringvej 59, 2600 Glostrup, Denmark article info abstract Article history: Extracellular UDP-glucose can activate the purinergic P2Y14 receptor. The aim of the present study Received 13 February 2014 was to examine the physiological importance of P2Y14 receptors in the vasculature. The data pre- Revised 13 May 2014 sented herein show that UDP-glucose causes contraction in mouse coronary and basilar arteries. Accepted 21 May 2014 The EC values and immunohistochemistry illustrated the strongest P2Y14 receptor expression in Available online 6 June 2014 50 the basilar artery. In the presence of pertussis toxin, UDP-glucose inhibited contraction in coronary Edited by Ned Mantei arteries and in the basilar artery it surprisingly caused relaxation. After organ culture of the coro- nary artery, the EC50 value decreased and an increased staining for the P2Y14 receptor was observed, showing receptor plasticity. Keywords: Purinergic receptors Ó 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. P2Y14 Coronary artery Basilar artery Receptor upregulation P2Y2 KO 1. Introduction vasoconstriction in porcine pancreatic arteries [12]. This study was designed to examine the physiological importance