Endocannabinoid-Based Therapies

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Daniele Piomelli ◽  
Alex Mabou Tagne
Keyword(s):  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Annual Review ◽  
Publication Date ◽  
Metabolizing Enzymes ◽  
Pharmacological Agents ◽  
Surface Receptors ◽  
Signaling Complex ◽  
Therapeutic Drugs ◽  
Pharmacology And Toxicology

The endocannabinoids are lipid-derived messengers that play a diversity of regulatory roles in mammalian physiology. Dysfunctions in their activity have been implicated in various disease conditions, attracting attention to the endocannabinoid system as a possible source of therapeutic drugs. This signaling complex has three components: the endogenous ligands, anandamide and 2-arachidonoyl- sn-glycerol (2-AG); a set of enzymes and transporters that generate, eliminate, or modify such ligands; and selective cell surface receptors that mediate their biological actions. We provide an overview of endocannabinoid formation, deactivation, and biotransformation and outline the properties and therapeutic potential of pharmacological agents that interfere with those processes. We describe small-molecule inhibitors that target endocannabinoid-producing enzymes, carrier proteins that transport the endocannabinoids into cells, and intracellular endocannabinoid-metabolizing enzymes. We briefly discuss selected agents that simultaneously interfere with components of the endocannabinoid system and with other functionally related signaling pathways. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Measuring Pharmacogene Variant Function at Scale Using Multiplexed Assays

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Renee C. Geck ◽  
Gabriel Boyle ◽  
Clara J. Amorosi ◽  
Douglas M. Fowler ◽  
Maitreya J. Dunham
Keyword(s):  
Next Generation Sequencing ◽  
Functional Data ◽  
Genetic Variants ◽  
Genetic Information ◽  
Annual Review ◽  
Publication Date ◽  
Drug Selection ◽  
Functional Consequences ◽  
Pharmacology And Toxicology ◽  
Generation Sequencing

As costs of next-generation sequencing decrease, identification of genetic variants has far outpaced our ability to understand their functional consequences. This lack of understanding is a central challenge to a key promise of pharmacogenomics: using genetic information to guide drug selection and dosing. Recently developed multiplexed assays of variant effect enable experimental measurement of the function of thousands of variants simultaneously. Here, we describe multiplexed assays that have been performed on nearly 25,000 variants in eight key pharmacogenes ( ADRB2, CYP2C9, CYP2C19, NUDT15, SLCO1B1, TMPT, VKORC1, and the LDLR promoter), discuss advances in experimental design, and explore key challenges that must be overcome to maximize the utility of multiplexed functional data. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Benjamin Steinhorn ◽  
Emrah Eroglu ◽  
Thomas Michel
Keyword(s):  
Dynamic Control ◽  
Cardiovascular Pharmacology ◽  
Redox Balance ◽  
Signaling Molecules ◽  
Annual Review ◽  
Publication Date ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Pharmacology And Toxicology ◽  
Intracellular Redox

Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Review of COVID-19 Antibody Therapies

2020 ◽  
Vol 50 (1) ◽  
Author(s):  
Jiahui Chen ◽  
Kaifu Gao ◽  
Rui Wang ◽  
Duc Duy Nguyen ◽  
Guo-Wei Wei
Keyword(s):  
Therapeutic Potential ◽  
Network Models ◽  
Data Bank ◽  
Topological Data Analysis ◽  
Annual Review ◽  
Publication Date ◽  
Binding Affinities ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Receptor

In the global health emergency caused by coronavirus disease 2019 (COVID-19), efficient and specific therapies are urgently needed. Compared with traditional small-molecular drugs, antibody therapies are relatively easy to develop; they are as specific as vaccines in targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and they have thus attracted much attention in the past few months. This article reviews seven existing antibodies for neutralizing SARS-CoV-2 with 3D structures deposited in the Protein Data Bank (PDB). Five 3D antibody structures associated with the SARS-CoV spike (S) protein are also evaluated for their potential in neutralizing SARS-CoV-2. The interactions of these antibodies with the S protein receptor-binding domain (RBD) are compared with those between angiotensin-converting enzyme 2 and RBD complexes. Due to the orders of magnitude in the discrepancies of experimental binding affinities, we introduce topological data analysis, a variety of network models, and deep learning to analyze the binding strength and therapeutic potential of the 14 antibody–antigen complexes. The current COVID-19 antibody clinical trials, which are not limited to the S protein target, are also reviewed. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 6, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

SARS-CoV-2 Neutralizing Antibodies for COVID-19 Prevention and Treatment

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Dapeng Li ◽  
Gregory D. Sempowski ◽  
Kevin O. Saunders ◽  
Priyamvada Acharya ◽  
Barton F. Haynes
Keyword(s):  
Neutralizing Antibodies ◽  
Antibody Therapy ◽  
Neutralizing Antibody ◽  
Annual Review ◽  
Publication Date ◽  
The Past ◽  
Therapeutic Drugs ◽  
Therapeutic Uses ◽  
The Us ◽  
Prevention And Treatment

Prophylactic and therapeutic drugs are urgently needed to combat coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over the past year, SARS-CoV-2 neutralizing antibodies have been developed for preventive or therapeutic uses. While neutralizing antibodies target the spike protein, their neutralization potency and breadth vary according to recognition epitopes. Several potent SARS-CoV-2 antibodies have shown degrees of success in preclinical or clinical trials, and the US Food and Drug Administration has issued emergency use authorization for two neutralizing antibody cocktails. Nevertheless, antibody therapy for SARS-CoV-2 still faces potential challenges, including emerging viral variants of concern that have antibody-escape mutations and the potential for antibody-mediated enhancement of infection or inflammation. This review summarizes representative SARS-CoV-2 neutralizing antibodies that have been reported and discusses prospects and challenges for the development of the next generation of COVID-19 preventive or therapeutic antibodies. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Thioredoxin Reductase Inhibition for Cancer Therapy

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Radosveta Gencheva ◽  
Elias S.J. Arnér
Keyword(s):  
Cancer Therapy ◽  
Thioredoxin Reductase ◽  
Normal Activity ◽  
Annual Review ◽  
Publication Date ◽  
Nadph Oxidases ◽  
Thioredoxin Reductase 1 ◽  
Wide Range ◽  
Oxidative Challenge ◽  
Pharmacology And Toxicology

The cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, TXNRD1), and to some extent mitochondrial TrxR2 (TXNRD2), can be inhibited by a wide range of electrophilic compounds. Many such compounds also yield cytotoxicity toward cancer cells in culture or in mouse models, and most compounds are likely to irreversibly modify the easily accessible selenocysteine residue in TrxR1, thereby inhibiting its normal activity to reduce cytosolic thioredoxin (Trx1, TXN) and other substrates of the enzyme. This leads to an oxidative challenge. In some cases, the inhibited forms of TrxR1 are not catalytically inert and are instead converted to prooxidant NADPH oxidases, named SecTRAPs, thus further aggravating the oxidative stress, particularly in cells expressing higher levels of the enzyme. In this review, the possible molecular and cellular consequences of these effects are discussed in relation to cancer therapy, with a focus on outstanding questions that should be addressed if targeted TrxR1 inhibition is to be further developed for therapeutic use. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Repurposing Colchicine for Heart Disease

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Nadia Bouabdallaoui ◽  
Jean-Claude Tardif
Keyword(s):  
Annual Review ◽  
Publication Date ◽  
Clinical Settings ◽  
Recurrent Pericarditis ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mediterranean Fever ◽  
Pharmacology And Toxicology ◽  
Artery Disease

Colchicine is one of the most ancient medications still prescribed. It is extracted from the Colchicum autumnale plant and is routinely used because of its broad anti-inflammatory properties to treat gout and familial Mediterranean fever. Colchicine has shown efficacy in various clinical settings in which inflammation is a key component, and it has become first-line therapy for acute and recurrent pericarditis. Two landmark clinical trials have recently shown that colchicine significantly improves cardiovascular outcomes on background statin and antiplatelet therapy in patients with coronary artery disease, supporting its role for the prevention of atherothrombotic events. Favorable results have also emerged in atrial fibrillation. We herein briefly review the most recent data related to the multiple cardiovascular conditions for which colchicine has been successfully repurposed. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Food Processing, Dysbiosis, Gastrointestinal Inflammatory Diseases, and Antiangiogenic Functional Foods or Beverages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jack N. Losso
Keyword(s):  
Mast Cells ◽  
Gut Microbiota ◽  
Food Processing ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Redox Homeostasis ◽  
Transglutaminase 2 ◽  
Janus Kinase ◽  
Annual Review ◽  
Publication Date

Foods and beverages provide nutrients and alter the gut microbiota, resulting in eubiosis or dysbiosis. Chronic consumption of a diet that is high in saturated or trans fats, meat proteins, reducing sugars, and salt and low in fiber induces dysbiosis. Dysbiosis, loss of redox homeostasis, mast cells, hypoxia, angiogenesis, the kynurenine pathway, transglutaminase 2, and/or the Janus kinase pathway are implicated in the pathogenesis and development of inflammatory bowel disease, celiac disease, and gastrointestinal malignancy. This review discusses the effects of oxidative, carbonyl, or glycative stress–inducing dietary ingredients or food processing–derived compounds on gut microbiota and gastrointestinal epithelial and mast cells as well as on the development of associated angiogenic diseases, including key signaling pathways. The preventive or therapeutic potential and the biochemical pathways of antiangiogenic or proangiogenic foods or beverages are also described. The outcomes of the interactions between disease pathways and components of food are critical for the design of foods and beverages for healthy lives. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 12 is March 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Thirty Years of Neuroscientific Investigation of Placebo and Nocebo: The Interesting, the Good, and the Bad

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Fabrizio Benedetti ◽  
Elisa Frisaldi ◽  
Aziz Shaibani
Keyword(s):  
Placebo Effect ◽  
Annual Review ◽  
Publication Date ◽  
Biological Mechanisms ◽  
The Past ◽  
Therapeutic Outcomes ◽  
Routine Medical Practice ◽  
Nocebo Effects ◽  
Pharmacology And Toxicology

Over the past 30 years there has been a surge of research on the placebo effect using a neuroscientific approach. The interesting aspects of this effort are related to the identification of several biological mechanisms of both the placebo and nocebo effects, the latter of which is defined as a negative placebo effect. Some important translational implications have emerged both in the setting of clinical trials and in routine medical practice. One of the principal contributions of neuroscience has been to draw the attention of the scientific and medical communities to the important role of psychobiological factors in therapeutic outcomes, be they drug related or not. Indeed, many biological mechanisms triggered by placebos and nocebos resemble those modulated by drugs, suggesting a possible interaction between psychological factors and drug action. Unfortunately, this new knowledge regarding placebos has the potential of being dangerously exploited by pseudoscience. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Introduction to the Theme “New Insights, Strategies, and Therapeutics for Common Diseases”

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Paul A. Insel ◽  
Terrence F. Blaschke ◽  
Susan G. Amara ◽  
Urs A. Meyer
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Strategies ◽  
Drug Formulation ◽  
Annual Review ◽  
Publication Date ◽  
Diverse Range ◽  
Common Diseases ◽  
Pharmacology And Toxicology ◽  
Patient Centric

The reviews in Volume 62 of the Annual Review of Pharmacology and Toxicology ( ARPT) cover a diverse range of topics. A theme that encompasses many of these reviews is their relevance to common diseases and disorders, including type 2 diabetes, heart failure, cancer, tuberculosis, Alzheimer's disease, neurodegenerative disorders, and Down syndrome. Other reviews highlight important aspects of therapeutics, including placebos and patient-centric approaches to drug formulation. The reviews with this thematic focus, as well as other reviews in this volume, emphasize new mechanistic insights, experimental and therapeutic strategies, and novel insights regarding topics in the disciplines of pharmacology and toxicology. As the editors of ARPT, we believe that these reviews help advance those disciplines and, even more importantly, have the potential to improve the health care of the world's population. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Pushing Forward the Future Tense: Perspectives of a Scientist

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lee E. Limbird
Keyword(s):  
Online Publication ◽  
Lessons Learned ◽  
Annual Review ◽  
Publication Date ◽  
Future Tense ◽  
The Future ◽  
Life Of The Mind ◽  
Pharmacology And Toxicology ◽  
The Mind ◽  
Scientific Life

This review is a somewhat chronological tale of my scientific life, emphasizing the why of the questions we asked in the lab and lessons learned that may be of value to nascent scientists. The reader will come to realize that the flow of my life has been driven by a combined life of the mind and life of the soul, intertwining like the strands of DNA. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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