Trends in pharmacological sciences
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Trends Pharmacol. Sci. · Aug 2020
ReviewTargeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19.
Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe coronavirus disease 2019 (COVID-19) might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. ⋯ JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.
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The calcitonin gene-related peptide (CGRP) receptor system has emerged as an important drug target for migraine. This is highlighted by the recent regulatory approval of the first drug targeting the CGRP signalling pathway, the CGRP receptor antibody erenumab. ⋯ G protein-coupled receptors (GPCRs) were thought to signal only at the cell surface, but it is now recognised that some GPCRs, including the CGRP receptor, undergo sustained signalling from endosomes, once internalised in response to ligand. What does this mean for drugs like erenumab? This review covers recent insights into the regulation of CGRP family receptors and examines what implications this may have on drug activity.
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Trends Pharmacol. Sci. · Jul 2016
ReviewHeteromeric α7β2 Nicotinic Acetylcholine Receptors in the Brain.
The α7 nicotinic acetylcholine receptor (α7 nAChR) is highly expressed in the brain, where it maintains various neuronal functions including (but not limited to) learning and memory. In addition, the protein expression levels of α7 nAChRs are altered in various brain disorders. ⋯ Interestingly, the α7β2 nAChR exhibits distinctive function and pharmacology from traditional homomeric α7 nAChRs. We review recent advances in probing the distribution, function, pharmacology, pathophysiology, and stoichiometry of the heteromeric α7β2 nAChR, which have provided new insights into the understanding of a novel target of cholinergic signaling.
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Trends Pharmacol. Sci. · Oct 2015
ReviewTherapeutic Targeting of Siglecs using Antibody- and Glycan-Based Approaches.
The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell type-specific expression pattern, endocytic properties, high expression on certain lymphomas/leukemias, and ability to modulate receptor signaling. ⋯ Several antibody-based therapies are in clinical trials and continue to be developed for the treatment of lymphoma/leukemia and autoimmune disease, while the therapeutic potential of glycan-based strategies for cargo delivery and immunomodulation is a promising new approach. Here we review these strategies with special emphasis on emerging approaches and disease areas that may benefit from targeting the Siglec family.
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Trends Pharmacol. Sci. · Sep 2015
ReviewApelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system.
Apelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. ⋯ To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced β-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental β-arrestin signalling. Proof-of-concept studies support the clinical potential for apelin receptor biased agonists.