Download or read book Characterization of Plasmodium Falciparum Choline Transporters written by and published by . This book was released on 2005 with total page 54 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum is the causative agent of severe human malaria. The rapid multiplication of the parasite within human red blood cells requires an active synthesis of new membranes. Choline analogs are potent antimalarial drugs. Although Choline transport has been suggested to be the target of these compounds, their exact mode of action is unknown. We identified two genes PfGAT and PfCTL1 as potential targets of these compounds. Here we report evidence that PfGAT encodes a Glycerol-3-phosphate acyltransferase enzyme responsible for the initial step of synthesis of P. falciparum membranes. Genetic data suggest that this pathway is essential for parasite survival and is a good target for development of new antimalarial drugs. We have also initiated a thorough genetic and biochemical characterization of PfCTL. Our data suggest that membrane proteins of the CTL family are not choline transporters. We generated transgenic parasites lacking PfCTL1, and showed that PfCTL is not essential for parasite intraerythrocytic development and survival. Finally we provide biochemical and genetic data suggesting that choline analogs act by specifically inhibiting phospholipid me%tabolism and the ability of the parasite to generate new membranes.

Download or read book Characterization of Plasmodium falciparum membrane transporters as potential antimalarial targets written by Stéphanie Bosne and published by . This book was released on 2014 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: La découverte de nouveaux agents antipaludiques est primordiale. A travers le monde, les chercheurs se sont focalisés sur plusieurs stratégies. Les plus développées sont : soit les tests de molécules issues de bibliothèques chimiques dans une recherche phénotypique (comme le test direct d'agents sur des cultures de parasites in vitro), soit la recherche de nouvelles molécules agissant sur l'activité d'une cible ou d'une voie spécifique et essentielle. Cette thèse est centrée sur le second type d'approche. Nous nous sommes intéressés aux transporteurs membranaires de P. falciparum. Pour cela, nous exprimons les protéines d'intérêt dans la levure et nous les purifions. Nous optimisons les tests fonctionnels, dans le but de : a) déterminer l'effet des molécules sur les cibles spécifiques ; b) tester leur effet sur les cultures d'érythrocytes infectés par P. falciparum in vitro ; c) vérifier leur toxicité sur des cellules de mammifères ; et d) réaliser le test des molécules les plus efficaces in vivo dans un modèle de paludisme murin. Notre travail actuel est focalisé sur l'ATPase6 de P. falciparum (PfATP6) et l'adénylate translocase (PfAdT), deux protéines membranaires essentielles localisées respectivement sur le réticulum endoplasmique et la membrane mitochondriale. Nous exprimons de manière hétérologue PfATP6 dans les membranes de levure, nous purifions la protéine et mesurons une activité ATPase spécifique. Nous avons ainsi pu tester une bibliothèque chimique importante et identifier des inhibiteurs spécifiques. Ces derniers ont ensuite été testés pour évaluer leur effet sur les stades érythrocytaires du parasite in vitro et leur cytotoxicité sur des cellules de mammifères. Pour le transporteur PfAdT, nous procédons comme pour PfATP6, mais nous avons choisi un autre type de test fonctionnel dans lequel la protéine est directement exprimée sur la membrane plasmique d'E. coli. Cela devrait permettre de mesurer le transport d'ATP radiomarqué, et l'identification d'inhibiteurs spécifiques dont les effets pourront être évalués sur des cultures de parasites in vitro et dans des essais de cytotoxicité.

Download or read book Characterization of PfFNT written by Janis Rambow and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Characterization of PfFNT written by and published by . This book was released on 2015 with total page 127 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Characterization of the Hexose Transporter of Plasmodium Falciparum written by and published by . This book was released on 2003 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Understanding Phospholipid Biosynthesis in the Human Malaria Parasite Plasmodium Falciparum Using Saccharomyces Cerevisiae as a Surrogate System written by Teresa C. Santiago and published by . This book was released on 2005 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Characterization of Plasmodium Falciparum Resistance to Novel Drugs written by Sonia Edayé and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Plasmodium falciparum is the deadly protozoan parasite responsible for malaria. Malaria is one of the most important infectious diseases that has been raging for millennia and affecting almost half of the world's population. The treatment regimen that was based on quinoline drugs such as chloroquine (CQ), was efficient for decades. Nowadays, the use of this class of drugs is doomed to failure due to the emergence of quinoline-resistant parasites. Today, artemisinin-based combination therapies (ACTs) are the first-line drugs for uncomplicated falciparum malaria treatment. ACTs improve the cure rate of malaria and thus are seen as efficient treatment against uncomplicated forms of the disease. Despite their efficiency, these drugs are currently facing the development of resistance. PfCRT and PfMDR1, which are membrane transporters, have been shown to be involved in malaria parasites drug resistance. To tackle the inefficiency of existing drugs in regard to the development of resistance, alternative therapies must be discovered. In this thesis, antimalarial activity of novel potential drugs against P. falciparum is assessed and the interaction of these drugs with PfCRT and PfMDR1 is determined. Furthermore, because many ABC transporter genes play a key role in drug resistance, the characterization of an ABC transporter member of the ABCG family in Plasmodium is addressed and its role in drug resistance investigated.In the first part of this thesis, MK571 (a quinoline analogue) activity against P. falciparum parasites is investigated. MK571 is found to be more toxic to most of the CQ-resistant strains than to the CQ-sensitive strains. In addition, we determine that MK571 is not a substrate of PfCRT as are other quinoline drugs, but is instead a substrate of PfMDR1. Therefore, it can be a good complement to existing quinoline drugs in the treatment of uncomplicated malaria. In the second part, novel compound analogues of chloroquine are tested for their antimalarial activity against CQ-sensitive and -resistant parasites. Although chloroquine analogues tested possess the quinoline ring structure of chloroquine, they are less efficient than chloroquine and are not substrates of PfCRT. One of the analogues (3-ICQ) reverses the resistance of CQ-resistant strains to chloroquine and therefore, could be used in combination with chloroquine in cases of CQ-resistant malaria. In the third part of the thesis we conduct the characterization of PfABCG, the sole member of the P. falciparum ABCG family. The characterization study demonstrates that PfABCG is localized on the parasite plasma membrane and is expressed throughout the asexual life cycle of the parasite. In addition, PfABCG is differentially expressed in various Plasmodium strains. This expression does not correlate with the resistance to chloroquine but to the sensitivity of the parasite to an antihistaminic drug named ketotifen. Overall, this thesis sheds light on challenges and understanding of the complex resistance machinery deployed by the P. falciparum parasite from novel drug discovery to characterization of proteins. " --

Download or read book Biochemistry and Molecular Biology of Parasites written by Joseph Marr and published by Elsevier. This book was released on 1995-09-06 with total page 363 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of parasitic organisms at the molecular level has yielded fascinating new insights of great medical, social, and economical importance, and has pointed the way for the treatment and prevention of the diseases they cause. Biochemistry and Molecular Biology of Parasites presents an up-to-date account of this modern scientific discipline in a manner that allows and encourages the reader to place the biochemistry and molecular biology of these organisms in their biological context. The chapters are cross-referenced and grouped in an arrangement that provides a fully integrated whole, and permits the reader to create a composite of the biochemical function of these organisms. Individual chapter includes those devoted to metabolism, in both aerobic and anaerobic protozoa; antioxidant mechanisms; parasite surfaces; organelles; invasion mechanisms; and chemotherapy. The helminths are discussed not only from the point of view of their cellular biochemistry and metabolism, but also with respect to both their integrated functions such as neurochemistry, structure and functions of surfaces, and reproduction. Written by expert investigators, this book will be of interest to all experienced researchers, graduate students, and to the newcomer eager to become familiar with the biochemistry and molecular biology of parasites.

Download or read book International Review of Cytology written by Kwang W. Jeon and published by Gulf Professional Publishing. This book was released on 2005-08-24 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: International Review of Cytology presents current advances and comprehensive reviews in cell biology - both plant and animal. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research. Articles in this volume address Redundancy of biological regulation as the basis for emergence of multidrug resistancedrug resistance; The palladin-myotilin-myopalladin family: Potent modulators of the actin cytoskeleton; Patch-clamp studies of the new permeability pathways in Plasmodium falciparum; Cellular mechanisms of bacterial internalization; Microinsemination and Transfer Using Male Germ Cells; Nuclear envelope, nuclear lamina in inherited diseases.

Download or read book The Blood brain Barrier written by William M. Pardridge and published by Lippincott Williams & Wilkins. This book was released on 1993 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: The characterization of the blood-brain barrier (BBB) is undergoing a paradigm shift as the century-old concept of a passive, impermeable barrier that segregates blood and brain interstitial fluid is giving way to the idea that the BBB is a dynamic conduit for the transport between blood and brain of those nutrients, peptides, proteins, or immune cells that have access to certain transport systems localized within the BBB membranes. This volume contains 20 contributed chapters organized in four parts: cell-cell interactions, subcellular organelle function, signal transduction mechanisms, and gene expression. There is also a foreword by the late W.H. Oldendorf (1925-1992) on the teleology of the blood-brain barrier and the survival advantage conferred upon the organism by its presence in the vertebrate brain. Annotation copyright by Book News, Inc., Portland, OR

Download or read book Comprehensive Analysis of Parasite Biology written by Sylke Müller and published by John Wiley & Sons. This book was released on 2016-10-10 with total page 574 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written and edited by experts in the field, this book brings together the current state of the art in phenotypic and rational, target-based approaches to drug discovery against pathogenic protozoa. The chapters focus particularly on virtual compounds and high throughput screening, natural products, computer-assisted drug design, structure-based drug design, mechanism of action identification, and pathway modelling. Furthermore, state-of the art "omics" technologies are described and currently studied enzymatic drug targets are discussed. Mathematical, systems biology-based approaches are introduced as new methodologies for dissecting complex aspects of pathogen survival mechanisms and for target identification. In addition, recently developed anti-parasitic agents targeting particular pathways, which serve as lead compounds for further drug development, are presented.

Download or read book Transport and Trafficking in the Malaria Infected Erythrocyte written by Gregory R. Bock and published by John Wiley & Sons. This book was released on 2008-04-30 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is an urgent need to uncover new therapies that will protect against malaria, as the parasite becomes increasingly resistant to available drugs and this book offers insights into three interrelated aspects of the malaria-infected erythrocyte: * The transport of solutes into and out of the infected cell and the use of specific trafficking pathways in drug targeting * The traffic of proteins produced by the intracellular parasite as an essential process for the biogenesis of transport systems. * The relationship between the transport of drugs into the infected cell and the mode of drug action and drug resistance.

Download or read book Membrane Transporters and Channels as Targets for Drugs written by Graça Soveral and published by Frontiers Media SA. This book was released on 2020-01-03 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transporters and channels are membrane proteins that mediate the traffic of metabolites, water and ions across biological membranes. Membrane transport proteins are crucial to maintain homeostasis and assure cell survival upon intracellular or environmental stress. A failure of any of these transport systems may have dramatic consequences for cell function. There is increasing evidence that membrane transport proteins play important functions in healthy conditions and that their absence or dysfunction may cause diseases. In recent years much attention has been paid to diseases resulting from defective transporters (“carrier diseases”) and ion channels (“channelopathies”). Very interestingly, altered expression of transporters has been described in several human pathologies. On this basis, many transport proteins are well acknowledged targets for drugs. Many others are involved in drug delivery and disposition and/or are considered potential targets. Others are off-targets for drugs and then, are responsible for side effects. Thus, membrane protein drug discovery is now an emerging field where the search for physiological mechanisms of regulation and for chemical compounds as modulators of transport activity, present new opportunities for drug development and for new therapies. This Research Topic addresses the latest research advances in membrane transport proteins, stimulating future research on these important protein families.

Download or read book Cambridge Scientific Biochemistry Abstracts written by and published by . This book was released on 1992 with total page 678 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Malaria Genome Projects written by Irwin W. Sherman and published by World Scientific. This book was released on 2012 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: The year 2012 marks the tenth anniversary of the announcement of the genome sequence of the human malaria parasite Plasmodium falciparum and that of its mosquito vector Anopheles. The genome sequences were a result of the Plasmodium falciparum Genome Project. This book covers in detail the biology of malaria parasites and the mosquitoes that transmit the disease, how the Genome Project came into being, the people who created it, and the cadre of scientists who are attempting to see the promise of the Project realized. The promise was: a more complete understanding of the genes of the parasite (and its vector) would provide a rational basis for the development of antimalarial drugs and vaccines, allow a better understanding of the regulation of the complex life cycle in the red blood and liver cells of the human, identify the genes the parasite uses to thwart the host immune response and the ways in which the parasite evades cure by drug treatments, as well as leading to more effective measures of control transmission. The hope was that cracking the genetic code of Plasmodium and Anopheles would reveal the biochemical Achilles heel of the parasite and its vector, leading to the development of novel drugs and better methods of control, and by finding the targets of protective immunity could result in the manufacture of effective vaccines. Through a historic approach, this book will allow for those new to the field, or those with insufficient background in the sciences, to have an easier entry point. Even scientists already working in the field may better appreciate how discoveries made in the past can impact the direction of future research.

Download or read book Apicomplexan Parasites written by Katja Becker and published by John Wiley & Sons. This book was released on 2011-01-19 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This handbook is the first dealing with the discovery of drugs directed against apicomplexan parasites. Amongst others, this group of endoparasites includes the causative agents of Malaria, Toxoplasmosis, and Babesiosis, the latter occurring mainly in animals. Written by renowned scientific experts from academia and industry, the book focuses on currentdrug development approaches for all apicomplexan diseases making it appealing to a large audience, ranging from research labs in academia to the human and veterinarian pharmaceutical industry. This work is the second volume of the new book series 'Drug Discovery in Infectious Diseases', edited by Prof. Dr Paul M. Selzer.

Download or read book Malaria Drugs Disease and Post genomic Biology written by David Sullivan and published by Springer Science & Business Media. This book was released on 2006-01-09 with total page 447 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite rapid increases in knowledge, malaria continues to kill more than a million people each year and causes symptomatic disease in a further 300 million individuals. This volume brings some of the world's best investigators to describe recent advances in both the scientific and clinical aspects of malaria, and bridges between the two.