Targeting Persistent Changes in Neuroimmune and Epigenetic Signaling in Adolescent Drinking to Treat Alcohol Use Disorder in Adulthood
Pharmacol Rev. 2023 Mar;75(2):380-396. doi: 10.1124/pharmrev.122.000710. Epub 2022 Dec 12.ABSTRACTStudies universally find early age of drinking onset is linked to lifelong risks of alcohol problems and alcohol use disorder (AUD). Assessment of the lasting effect of drinking during adolescent development in humans is confounded by the diversity of environmental and genetic factors that affect adolescent development, including emerging personality disorders and progressive increases in drinking trajectories into adulthood. Preclinical studies using an adolescent intermittent ethanol (AIE) exposure rat model of underage bing...
Source: Pharmacognosy Reviews - February 13, 2023 Category: Drugs & Pharmacology Authors: Fulton T Crews Leon G Coleman Victoria A Macht Ryan P Vetreno Source Type: research
Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review
Pharmacol Rev. 2023 Mar;75(2):309-327. doi: 10.1124/pharmrev.122.000665. Epub 2022 Dec 12.ABSTRACTAmong different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Express...
Source: Pharmacognosy Reviews - February 13, 2023 Category: Drugs & Pharmacology Authors: Edris Choupani Mohammad Mahmoudi Gomari Saeed Zanganeh Sherko Nasseri Kaveh Haji-Allahverdipoor Neda Rostami Yaeren Hernandez Safa Najafi Neda Saraygord-Afshari Arshad Hosseini Source Type: research
Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins
Pharmacol Rev. 2023 Jan;75(1):1-34. doi: 10.1124/pharmrev.120.000180. Epub 2022 Dec 8.ABSTRACTG protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR-RAMP inte...
Source: Pharmacognosy Reviews - February 9, 2023 Category: Drugs & Pharmacology Authors: Ilana B Kotliar Emily Lorenzen Jochen M Schwenk Debbie L Hay Thomas P Sakmar Source Type: research
Dopamine, Immunity, and Disease
Pharmacol Rev. 2023 Jan;75(1):62-158. doi: 10.1124/pharmrev.122.000618. Epub 2022 Dec 8.ABSTRACTThe neurotransmitter dopamine is a key factor in central nervous system (CNS) function, regulating many processes including reward, movement, and cognition. Dopamine also regulates critical functions in peripheral organs, such as blood pressure, renal activity, and intestinal motility. Beyond these functions, a growing body of evidence indicates that dopamine is an important immunoregulatory factor. Most types of immune cells express dopamine receptors and other dopaminergic proteins, and many immune cells take up, produce, stor...
Source: Pharmacognosy Reviews - February 9, 2023 Category: Drugs & Pharmacology Authors: Breana Channer Stephanie M Matt Emily A Nickoloff-Bybel Vasiliki Pappa Yash Agarwal Jason Wickman Peter J Gaskill Source Type: research
Pharmacological Modulation of the Crosstalk between Aberrant Janus Kinase Signaling and Epigenetic Modifiers of the Histone Deacetylase Family to Treat Cancer
Pharmacol Rev. 2023 Jan;75(1):35-61. doi: 10.1124/pharmrev.122.000612. Epub 2022 Dec 8.ABSTRACTHyperactivated Janus kinase (JAK) signaling is an appreciated drug target in human cancers. Numerous mutant JAK molecules as well as inherent and acquired drug resistance mechanisms limit the efficacy of JAK inhibitors (JAKi). There is accumulating evidence that epigenetic mechanisms control JAK-dependent signaling cascades. Like JAKs, epigenetic modifiers of the histone deacetylase (HDAC) family regulate the growth and development of cells and are often dysregulated in cancer cells. The notion that inhibitors of histone deacetyl...
Source: Pharmacognosy Reviews - February 8, 2023 Category: Drugs & Pharmacology Authors: Al-Hassan M Mustafa Oliver H Kr ämer Source Type: research
Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning
Pharmacol Rev. 2023 Jan;75(1):159-216. doi: 10.1124/pharmrev.121.000348. Epub 2022 Dec 8.ABSTRACTPreconditioning, postconditioning, and remote conditioning of the myocardium enhance the ability of the heart to withstand a prolonged ischemia/reperfusion insult and the potential to provide novel therapeutic paradigms for cardioprotection. While many signaling pathways leading to endogenous cardioprotection have been elucidated in experimental studies over the past 30 years, no cardioprotective drug is on the market yet for that indication. One likely major reason for this failure to translate cardioprotection into patient be...
Source: Pharmacognosy Reviews - February 8, 2023 Category: Drugs & Pharmacology Authors: P éter Ferdinandy Ioanna Andreadou Gary F Baxter Hans Erik B øtker Sean M Davidson Dobromir Dobrev Bernard J Gersh Gerd Heusch Sandrine Lecour Marisol Ruiz-Meana Coert J Zuurbier Derek J Hausenloy Rainer Schulz Source Type: research
Cellular Senescence: From Mechanisms to Current Biomarkers and Senotherapies
Pharmacol Rev. 2023 Jul;75(4):675-713. doi: 10.1124/pharmrev.122.000622. Epub 2023 Feb 2.ABSTRACTAn increase in life expectancy in developed countries has led to a surge of chronic aging-related diseases. In the last few decades, several studies have provided evidence of the prominent role of cellular senescence in many of these pathologies. Key traits of senescent cells include cell cycle arrest, apoptosis resistance, and secretome shift to senescence-associated secretory phenotype resulting in increased secretion of various intermediate bioactive factors important for senescence pathophysiology. However, cellular senesce...
Source: Pharmacognosy Reviews - February 2, 2023 Category: Drugs & Pharmacology Authors: Vasco Lucas Cl áudia Cavadas C élia Alexandra Aveleira Source Type: research
Advances in Nanozymes as a Paradigm for Viral Diagnostics and Therapy
Pharmacol Rev. 2023 Jul;75(4):739-757. doi: 10.1124/pharmrev.122.000719. Epub 2023 Jan 27.ABSTRACTOver the past few decades, humankind has constantly encountered new viral species that create havoc in the socioeconomic balance worldwide. Among the method to combat these novel viral infections, fast and point-of-care diagnosis is of prime importance to contain the spreading of viral infections. However, most sensitive diagnostic systems for viral infections are time-consuming and require well-trained professionals, making it difficult for the patients. In recent years nanozymes emerged as promising therapeutic and fast diag...
Source: Pharmacognosy Reviews - January 27, 2023 Category: Drugs & Pharmacology Authors: Garima Sharma Srijan Chatterjee Chiranjib Chakraborty Jin-Chul Kim Source Type: research
Pharmacological Inhibition of the NLRP3 Inflammasome: Structure, Molecular Activation, and Inhibitor-NLRP3 Interaction
Pharmacol Rev. 2023 May;75(3):487-520. doi: 10.1124/pharmrev.122.000629. Epub 2023 Jan 20.ABSTRACTThe nucleotide-binding, oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein complex that combines sensing, regulation, and effector functions to regulate inflammation in health and disease. NLRP3 is activated by a diverse range of inflammation-instigating signals known as pathogen associated molecular patterns and danger associated molecular patterns. Upon activation, NLRP3 oligomerizes and recruits partner proteins to form a supramolecular platform to process the matura...
Source: Pharmacognosy Reviews - January 20, 2023 Category: Drugs & Pharmacology Authors: Qiang Ma Source Type: research
Understanding the Neural Mechanisms of General Anesthesia from Interaction with Sleep-Wake State: A Decade of Discovery
Pharmacol Rev. 2023 May;75(3):532-553. doi: 10.1124/pharmrev.122.000717. Epub 2023 Jan 10.ABSTRACTThe development of cutting-edge techniques to study specific brain regions and neural circuits that regulate sleep-wake brain states and general anesthesia (GA), has increased our understanding of these states that exhibit similar neurophysiologic traits. This review summarizes current knowledge focusing on cell subtypes and neural circuits that control wakefulness, rapid eye movement (REM) sleep, non-REM sleep, and GA. We also review novel insights into their interactions and raise unresolved questions and challenges in this ...
Source: Pharmacognosy Reviews - January 10, 2023 Category: Drugs & Pharmacology Authors: Wei-Wei Bao Shan Jiang Wei-Min Qu Wen-Xian Li Chang-Hong Miao Zhi-Li Huang Source Type: research
Turn On, Tune In, Turnover! Target Biology Impacts In Vivo Potency, Efficacy, and Clearance
We describe (i) new (open model) expressions of the in vivo potency and efficacy parameters, which embody target turnover, binding, and complex kinetics, also capturing full, partial, and inverse agonism and antagonism; (ii) a detailed examination of open models to show what potency and efficacy parameters have in common and how they differ; and (iii) a comprehensive literature review showing that target turnover rate varies with age, species, tissue/subregion, treatment, disease state, hormonal and nutritional state, and day-night cycle. The new open model expression, which integrates system and drug properties, shows the...
Source: Pharmacognosy Reviews - January 10, 2023 Category: Drugs & Pharmacology Authors: Johan Gabrielsson Stephan Hjorth Source Type: research
Time to Change: A Systems Pharmacology Approach to Disentangle Mechanisms of Drug-Induced Mitochondrial Toxicity
Pharmacol Rev. 2023 May;75(3):463-486. doi: 10.1124/pharmrev.122.000568. Epub 2023 Jan 10.ABSTRACTAn increasing number of commonly prescribed drugs are known to interfere with mitochondrial function, which is associated with almost half of all Food and Drug Administration black box warnings, a variety of drug withdrawals, and attrition of drug candidates. This can mainly be attributed to a historic lack of sensitive and specific assays to identify the mechanisms underlying mitochondrial toxicity during drug development. In the last decade, a better understanding of drug-induced mitochondrial dysfunction has been achieved b...
Source: Pharmacognosy Reviews - January 10, 2023 Category: Drugs & Pharmacology Authors: Charlotte A Hoogstraten Jonathan J Lyon Jan A M Smeitink Frans G M Russel Tom J J Schirris Source Type: research
Sulfotransferase 2B1b, Sterol Sulfonation, and Disease
Pharmacol Rev. 2023 May;75(3):521-531. doi: 10.1124/pharmrev.122.000679. Epub 2022 Dec 22.ABSTRACTThe primary function of human sulfotransferase 2B1b (SULT2B1b) is to sulfonate cholesterol and closely related sterols. SULT2B1b sterols perform a number of essential cellular functions. Many are signaling molecules whose activities are redefined by sulfonation-allosteric properties are switched "on" or "off," agonists are transformed into antagonists, and vice versa. Sterol sulfonation is tightly coupled to cholesterol homeostasis, and sulfonation imbalances are causally linked to cholesterol-related diseases including certai...
Source: Pharmacognosy Reviews - December 22, 2022 Category: Drugs & Pharmacology Authors: Ian Cook Thomas S Leyh Source Type: research
Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications
Pharmacol Rev. 2023 Mar;75(2):263-308. doi: 10.1124/pharmrev.122.000654. Epub 2022 Dec 22.ABSTRACTLysine-selective molecular tweezers (MTs) are supramolecular host molecules displaying a remarkably broad spectrum of biologic activities. MTs act as inhibitors of the self-assembly and toxicity of amyloidogenic proteins using a unique mechanism. They destroy viral membranes and inhibit infection by enveloped viruses, such as HIV-1 and SARS-CoV-2, by mechanisms unrelated to their action on protein self-assembly. They also disrupt biofilm of Gram-positive bacteria. The efficacy and safety of MTs have been demonstrated in vitro,...
Source: Pharmacognosy Reviews - December 22, 2022 Category: Drugs & Pharmacology Authors: Hedieh Shahpasand-Kroner Ibrar Siddique Ravinder Malik Gabriel R Linares Magdalena I Ivanova Justin Ichida Tatjana Weil Jan M ünch Elsa Sanchez-Garcia Frank-Gerrit Kl ärner Thomas Schrader Gal Bitan Source Type: research
Opportunities for Nitric Oxide in Potentiating Cancer Immunotherapy
Pharmacol Rev. 2022 Oct;74(4):1146-1175. doi: 10.1124/pharmrev.121.000500.ABSTRACTDespite nearly 30 years of development and recent highlights of nitric oxide (NO) donors and NO delivery systems in anticancer therapy, the limited understanding of exogenous NO's effects on the immune system has prevented their advancement into clinical use. In particular, the effects of exogenously delivered NO differing from that of endogenous NO has obscured how the potential and functions of NO in anticancer therapy may be estimated and exploited despite the accumulating evidence of NO's cancer therapy-potentiating effects on the immune ...
Source: Pharmacognosy Reviews - September 30, 2022 Category: Drugs & Pharmacology Authors: Jihoon Kim Susan N Thomas Source Type: research
