Opportunities for Host-targeted Therapies for Malaria
Elizabeth K.K. Glennon,Elizabeth K.K. Glennon,Selasi Dankwa,Joseph D. Smith,Joseph D. Smith,Alexis Kaushansky,Alexis Kaushansky +6 more
TLDR
New opportunities for host-targeted therapeutics for malaria and the potential to harness drug polypharmacology to simultaneously target multiple host pathways using a single drug intervention are discussed.About:
This article is published in Trends in Parasitology.The article was published on 2018-10-01 and is currently open access. It has received 41 citations till now. The article focuses on the topics: Plasmodium vivax & Cerebral Malaria.read more
Citations
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Ferrocene-Based Compounds with Antimalaria/Anticancer Activity
TL;DR: This review will be focused on compounds with ferrocene moieties that exhibit either an anticancer or antimalarial activity.
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Blood-Brain Barrier in Cerebral Malaria: Pathogenesis and Therapeutic Intervention.
TL;DR: The mechanisms associated with the disruption of the BBB are reviewed and the current, still limited, knowledge on the contribution of different cell types, microparticles, and the kynurenine pathway in the regulation of BBB dysfunction is discussed, and how these molecules could be used as potential new therapeutic targets.
Journal ArticleDOI
Discovery of Druggable Host Factors Critical to Plasmodium Liver-Stage Infection.
TL;DR: It is revealed that various host intracellular protein trafficking pathways are subverted by Plasmodium parasites during the liver stage and provide new insights into their manipulation for growth and development.
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Brain Endothelium: The “Innate Immunity Response Hypothesis” in Cerebral Malaria Pathogenesis
TL;DR: Uncovering mechanisms of BVE involvement in sensing Plasmodium infection, recruiting of immune cells and directing immune effector functions could reveal pharmacological targets to promote BBB protection with potential applications in CM clinical management.
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Development of Chemical Entities Endowed with Potent Fast-Killing Properties against Plasmodium falciparum Malaria Parasites.
Alexios N Matralis,Adnan Malik,Maria Penzo,Maria Penzo,Inmaculada Moreno,Maria Jesus Almela,Isabel Camino,Benigno Crespo,Anas Saadeddin,Sonja Ghidelli-Disse,Lourdes Rueda,Félix Calderón,Simon A. Osborne,Gerard Drewes,Markus Boesche,Elena Fernández-Álvaro,Jose Ignacio Martin Hernando,David A. Baker +17 more
TL;DR: The medicinal chemistry efforts focused on a cGMP-dependent protein kinase (PKG) inhibitor scaffold are described, leading to the identification of novel chemical entities with very potent, similar to artemisinins, fast-killing potency against asexual blood stages that cause disease, and activity against gametocyte activation that is required for transmission.
References
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Journal ArticleDOI
Endoplasmic reticulum stress in liver disease
Harmeet Malhi,Randal J. Kaufman +1 more
TL;DR: The unfolded protein response is activated in several liver diseases; including obesity associated fatty liver disease, viral hepatitis, and alcohol-induced liver injury, raising the possibility that ER stress-dependent alteration in lipid homeostasis is the mechanism that underlies the steatosis.
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A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group.
José A. Stoute,Moncef Mohamed Slaoui,D. G. Heppner,P Momin,Kent E. Kester,P Desmons,Bruce T. Wellde,Nathalie Garcon,Urszula Krzych,M Marchand +9 more
TL;DR: A recombinant vaccine based on fusion of the circumsporozoite protein and HBsAg plus a potent adjuvant can protect against experimental challenge with P. falciparum malaria.
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TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria.
Dominic P. Kwiatkowski,Adrian V. S. Hill,I. Sambou,P. Twumasi,J. Castracane,K. R. Manogue,Anthony Cerami,David Brewster,Brian Greenwood +8 more
TL;DR: It is concluded that increased TNF production is a normal host response to P falciparum infection, but that excessive levels of production may predispose to cerebral malaria and a fatal outcome.
Journal ArticleDOI
Tumor Necrosis Factor and Disease Severity in Children with Falciparum Malaria
Georges E. Grau,Terrie E. Taylor,Malcolm E. Molyneux,Jack J. Wirima,Pierre Vassalli,Marcel Hommel,Paul-Henri Lambert +6 more
TL;DR: The level of tumor necrosis factor is frequently increased in patients with severe falciparum malaria, particularly in those with cerebral malaria or hypoglycemia, and whether it is important in the pathogenesis of the signs and symptoms of the disease requires further study.
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Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity
TL;DR: Quantitative analysis revealed complex and often unexpected interactions between protein kinases and kinase inhibitors, with a wide spectrum of promiscuity, revealing how large-scale profiling can identify multitargeted inhibitors of specific, diverse kinases.
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Host Scavenger Receptor SR-BI Plays a Dual Role in the Establishment of Malaria Parasite Liver Infection
Cristina Rodrigues,Michael Hannus,Miguel Prudêncio,Miguel Prudêncio,Cecilie Martin,Lígia A. Gonçalves,Silvia Portugal,Sabrina Epiphanio,Akin Akinc,Philipp Hadwiger,Kerstin Jahn-Hofmann,Ingo Röhl,Geert-Jan van Gemert,Jean-François Franetich,Adrian J. F. Luty,Robert Sauerwein,Dominique Mazier,Victor Koteliansky,Hans-Peter Vornlocher,Christophe Echeverri,Maria M. Mota,Maria M. Mota +21 more