Pharmacological Regulation of Endoplasmic Reticulum Structure and Calcium Dynamics: Importance for Neurodegenerative Diseases
Pharmacol Rev. 2023 Sep;75(5):959-978. doi: 10.1124/pharmrev.122.000701. Epub 2023 May 1.ABSTRACTThe endoplasmic reticulum (ER) is the largest organelle of the cell, composed of a continuous network of sheets and tubules, and is involved in protein, calcium (Ca2+), and lipid homeostasis. In neurons, the ER extends throughout the cell, both somal and axodendritic compartments, and is highly important for neuronal functions. A third of the proteome of a cell, secreted and membrane-bound proteins, are processed within the ER lumen and most of these proteins are vital for neuronal activity. The brain itself is high in lipid co...
Source: Pharmacognosy Reviews - May 1, 2023 Category: Drugs & Pharmacology Authors: Ilmari Parkkinen Anna Their Muhammad Yasir Asghar Sreesha Sree Eija Jokitalo Mikko Airavaara Source Type: research
< em > β < /em > -Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives
Pharmacol Rev. 2023 Sep;75(5):854-884. doi: 10.1124/pharmrev.121.000302. Epub 2023 Apr 7.ABSTRACTThe two β-arrestins, β-arrestin-1 and -2 (systematic names: arrestin-2 and -3, respectively), are multifunctional intracellular proteins that regulate the activity of a very large number of cellular signaling pathways and physiologic functions. The two proteins were discovered for their ability to disrupt signaling via G protein-coupled receptors (GPCRs) via binding to the activated receptors. However, it is now well recognized that both β-arrestins can also act as direct modulators of numerous cellular processes via either ...
Source: Pharmacognosy Reviews - April 7, 2023 Category: Drugs & Pharmacology Authors: J ürgen Wess Antwi-Boasiako Oteng Osvaldo Rivera-Gonzalez Eugenia V Gurevich Vsevolod V Gurevich Source Type: research
ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery
Pharmacol Rev. 2023 Sep;75(5):815-853. doi: 10.1124/pharmrev.120.000025. Epub 2023 Mar 27.ABSTRACTThe drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat central nervous system (CNS) diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solving this clinical problem.In this comprehensive review, we summarize current knowledge on signaling pathway...
Source: Pharmacognosy Reviews - March 27, 2023 Category: Drugs & Pharmacology Authors: Julia A Schulz Anika M S Hartz Bj örn Bauer Source Type: research
Pharmacogenomics: Driving Personalized Medicine
Pharmacol Rev. 2023 Jul;75(4):789-814. doi: 10.1124/pharmrev.122.000810. Epub 2023 Mar 16.ABSTRACTPersonalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool to improve outcomes and prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all "-omics" fields (e.g., proteomics, transcriptomics, metabolomics, and metagenomics). This review summarizes basic genomics principles relevant to translation into therapies, assessing pharmac...
Source: Pharmacognosy Reviews - March 17, 2023 Category: Drugs & Pharmacology Authors: Wolfgang Sadee Danxin Wang Katherine Hartmann Amanda Ewart Toland Source Type: research
Review of Natural Language Processing in Pharmacology
Pharmacol Rev. 2023 Jul;75(4):714-738. doi: 10.1124/pharmrev.122.000715. Epub 2023 Mar 17.ABSTRACTNatural language processing (NLP) is an area of artificial intelligence that applies information technologies to process the human language, understand it to a certain degree, and use it in various applications. This area has rapidly developed in the past few years and now employs modern variants of deep neural networks to extract relevant patterns from large text corpora. The main objective of this work is to survey the recent use of NLP in the field of pharmacology. As our work shows, NLP is a highly relevant information ext...
Source: Pharmacognosy Reviews - March 17, 2023 Category: Drugs & Pharmacology Authors: Dimitar Trajanov Vangel Trajkovski Makedonka Dimitrieva Jovana Dobreva Milos Jovanovik Matej Klemen Ale š Žagar Marko Robnik- Šikonja Source Type: research
G Protein-Coupled Receptor Pharmacology-Insights from Mass Spectrometry
We describe the utility of MS, including HDX-MS and native-MS, in investigating GPCR pharmacology. Specifically, we include ligand-drug interactions and Gi/s protein coupling and illustrate how these techniques can lead to the discovery of endogenous allosteric ligands and thereby offer a new perspective for drug discovery of GPCRs. SIGNIFICANCE STATEMENT: GPCRs are the largest and most diverse group of membrane receptors in eukaryotes. To carry out signaling, GPCRs adopt a range of conformational states to elicit G-protein coupling or arrestin binding. Because of their conformational dynamics, GPCRs remain challenging to ...
Source: Pharmacognosy Reviews - March 14, 2023 Category: Drugs & Pharmacology Authors: Hsin-Yung Yen Ali Jazayeri Carol V Robinson Source Type: research
Potassium Channels in Parkinson's Disease: Potential Roles in Its Pathogenesis and Innovative Molecular Targets for Treatment
Pharmacol Rev. 2023 Jul;75(4):758-788. doi: 10.1124/pharmrev.122.000743. Epub 2023 Mar 14.ABSTRACTParkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the midbrain. The loss of neurons results in a subsequent reduction of dopamine in the striatum, which underlies the core motor symptoms of PD. To date, there are no effective treatments to stop, slow, or reverse the pathologic progression of dopaminergic neurodegeneration. This unfortunate predicament is because of the current early stages in understanding the ...
Source: Pharmacognosy Reviews - March 14, 2023 Category: Drugs & Pharmacology Authors: Xiaoyi Chen Yunjiang Feng Ronald J Quinn Dean L Pountney Des R Richardson George D Mellick Linlin Ma Source Type: research
Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders
Pharmacol Rev. 2023 Jul;75(4):554-674. doi: 10.1124/pharmrev.121.000523. Epub 2023 Mar 14.ABSTRACTOveractive bladder syndrome with and without urinary incontinence and related conditions, signs, and disorders such as detrusor overactivity, neurogenic lower urinary tract dysfunction, underactive bladder, stress urinary incontinence, and nocturia are common in the general population and have a major impact on the quality of life of the affected patients and their partners. Based on the deliberations of the subcommittee on pharmacological treatments of the 7th International Consultation on Incontinence, we present a comprehen...
Source: Pharmacognosy Reviews - March 14, 2023 Category: Drugs & Pharmacology Authors: Martin C Michel Linda Cardozo Christopher J Chermansky Francisco Cruz Yasuhiko Igawa Kyu-Sung Lee Arun Sahai Alan J Wein Karl-Erik Andersson Source Type: research
Pharmacology of Heparin and Related Drugs: An Update
This article provides an update on our previous review with more recent developments and observations made for these novel uses of heparin and an overview of the development status of heparin-based drugs. SIGNIFICANCE STATEMENT: This state-of-the-art review covers recent developments in the use of heparin and heparin-like materials as anticoagulant, now including immunothrombosis observations, and as nonanticoagulant including a role in the treatment of SARS-coronavirus and inflammatory conditions.PMID:36792365 | DOI:10.1124/pharmrev.122.000684 (Source: Pharmacognosy Reviews)
Source: Pharmacognosy Reviews - February 15, 2023 Category: Drugs & Pharmacology Authors: John Hogwood Barbara Mulloy Rebeca Lever Elaine Gray Clive P Page Source Type: research
Neural Mechanisms and Psychology of Psychedelic Ego Dissolution
Pharmacol Rev. 2022 Oct;74(4):876-917. doi: 10.1124/pharmrev.121.000508.ABSTRACTNeuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organization and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5-HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message-passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics: in particular, t...
Source: Pharmacognosy Reviews - February 14, 2023 Category: Drugs & Pharmacology Authors: Devon Stoliker Gary F Egan Karl J Friston Adeel Razi Source Type: research
Changing Cerebral Blood Flow, Glucose Metabolism, and Dopamine Binding Through Transcranial Magnetic Stimulation: A Systematic Review of Transcranial Magnetic Stimulation-Positron Emission Tomography Literature
Pharmacol Rev. 2022 Oct;74(4):918-932. doi: 10.1124/pharmrev.122.000579.ABSTRACTTranscranial magnetic stimulation (TMS) is a noninvasive neuromodulation tool currently used as a treatment in multiple psychiatric and neurologic disorders. Despite its widespread use, we have an incomplete understanding of the way in which acute and chronic sessions of TMS affect various neural and vascular systems. This systematic review summarizes the state of our knowledge regarding the effects TMS may be having on cerebral blood flow, glucose metabolism, and neurotransmitter release. Forty-five studies were identified. Several key themes ...
Source: Pharmacognosy Reviews - February 13, 2023 Category: Drugs & Pharmacology Authors: Kaitlin R Kinney Colleen A Hanlon Source Type: research
Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies
Pharmacol Rev. 2022 Oct;74(4):933-961. doi: 10.1124/pharmrev.122.000583.ABSTRACTGlycine receptors are ligand-gated ion channels that mediate synaptic inhibition throughout the mammalian spinal cord, brainstem, and higher brain regions. They have recently emerged as promising targets for novel pain therapies due to their ability to produce antinociception by inhibiting nociceptive signals within the dorsal horn of the spinal cord. This has greatly enhanced the interest in developing positive allosteric modulators of glycine receptors. Several pharmaceutical companies and research facilities have attempted to identify new th...
Source: Pharmacognosy Reviews - February 13, 2023 Category: Drugs & Pharmacology Authors: Casey I Gallagher Damien A Ha Robert J Harvey Robert J Vandenberg Source Type: research
Exploring Intestinal Surface Receptors in Oral Nanoinsulin Delivery
Pharmacol Rev. 2022 Oct;74(4):962-983. doi: 10.1124/pharmrev.122.000631.ABSTRACTSubcutaneous and inhaled insulins are associated with needle phobia, lipohypertrophy, lipodystrophy, and cough in diabetes treatment. Oral nanoinsulin has been developed, reaping the physiologic benefits of peroral administration. This review profiles intestinal receptors exploitable in targeted delivery of oral nanoinsulin. Intestinal receptor targeting improves oral insulin bioavailability and sustains blood glucose-lowering response. Nonetheless, these studies are conducted in small animal models with no optimization of insulin dose, targeti...
Source: Pharmacognosy Reviews - February 13, 2023 Category: Drugs & Pharmacology Authors: Carlynne Choy Lee Yong Lim Lai Wah Chan Zhixiang Cui Shirui Mao Tin Wui Wong Source Type: research
Pharmacological Targeting of Mitochondria in Diabetic Kidney Disease
Pharmacol Rev. 2023 Mar;75(2):250-262. doi: 10.1124/pharmrev.122.000560. Epub 2022 Dec 12.ABSTRACTDiabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in the United States and many other countries. DKD occurs through a variety of pathogenic processes that are in part driven by hyperglycemia and glomerular hypertension, leading to gradual loss of kidney function and eventually progressing to ESRD. In type 2 diabetes, chronic hyperglycemia and glomerular hyperfiltration leads to glomerular and proximal tubular dysfunction. Simultaneously, mitochondrial dysfunction occurs in the early stages of...
Source: Pharmacognosy Reviews - February 13, 2023 Category: Drugs & Pharmacology Authors: Kristan H Cleveland Rick G Schnellmann Source Type: research
Sex/Gender Differences in the Time-Course for the Development of Substance Use Disorder: A Focus on the Telescoping Effect
Pharmacol Rev. 2023 Mar;75(2):217-249. doi: 10.1124/pharmrev.121.000361. Epub 2022 Dec 12.ABSTRACTSex/gender effects have been demonstrated for multiple aspects of addiction, with one of the most commonly cited examples being the "telescoping effect" where women meet criteria and/or seek treatment of substance use disorder (SUD) after fewer years of drug use as compared with men. This phenomenon has been reported for multiple drug classes including opioids, psychostimulants, alcohol, and cannabis, as well as nonpharmacological addictions, such as gambling. However, there are some inconsistent reports that show either no di...
Source: Pharmacognosy Reviews - February 13, 2023 Category: Drugs & Pharmacology Authors: Eleanor Blair Towers Ivy L Williams Emaan I Qillawala Emilie F Rissman Wendy J Lynch Source Type: research
