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Molecular Activation of NLRP3 Inflammasome by Particles and Crystals: A Continuing Challenge of Immunology and Toxicology
Annu Rev Pharmacol Toxicol. 2023 Sep 14. doi: 10.1146/annurev-pharmtox-031023-125300. Online ahead of print.ABSTRACTParticles and crystals constitute a unique class of toxic agents that humans are constantly exposed to both endogenously and from the environment. Deposition of particulates in the body is associated with a range of diseases and toxicity. The mechanism by which particulates cause disease remains poorly understood due to the lack of mechanistic insights into particle-biological interactions. Recent research has revealed that many particles and crystals activate the NLRP3 inflammasome, an intracellular pattern-...
Source: Annual Review of Pharmacology and Toxicology - September 14, 2023 Category: Drugs & Pharmacology Authors: Qiang Ma Chol Seung Lim Source Type: research

Translational In Vivo Assays in Behavioral Biology
Annu Rev Pharmacol Toxicol. 2023 Sep 14. doi: 10.1146/annurev-pharmtox-051921-093711. Online ahead of print.ABSTRACTThe failure of preclinical research to advance successful candidate medications in psychiatry has created a paradigmatic crisis in psychiatry. The Research Domain Criteria (RDoC) initiative was designed to remedy this situation with a neuroscience-based approach that employs multimodal and cross-species in vivo methodology to increase the probability of translational findings and, consequently, drug discovery. The present review underscores the feasibility of this methodological approach by briefly reviewing,...
Source: Annual Review of Pharmacology and Toxicology - September 14, 2023 Category: Drugs & Pharmacology Authors: Sarah L Withey Diego A Pizzagalli Jack Bergman Source Type: research

Orexin Receptor Antagonism: Normalizing Sleep Architecture in Old Age and Disease
Annu Rev Pharmacol Toxicol. 2023 Sep 14. doi: 10.1146/annurev-pharmtox-040323-031929. Online ahead of print.ABSTRACTSleep is essential for human well-being, yet the quality and quantity of sleep reduce as age advances. Older persons (>65 years old) are more at risk of disorders accompanied and/or exacerbated by poor sleep. Furthermore, evidence supports a bidirectional relationship between disrupted sleep and Alzheimer's disease (AD) or related dementias. Orexin/hypocretin neuropeptides stabilize wakefulness, and several orexin receptor antagonists (ORAs) are approved for the treatment of insomnia in adults. Dysregulati...
Source: Annual Review of Pharmacology and Toxicology - September 14, 2023 Category: Drugs & Pharmacology Authors: Jarrah O-Z J Kron Ryan J Keenan Daniel Hoyer Laura H Jacobson Source Type: research

G Protein-Coupled Receptor Signaling: New Insights Define Cellular Nanodomains
Annu Rev Pharmacol Toxicol. 2023 Sep 8. doi: 10.1146/annurev-pharmtox-040623-115054. Online ahead of print.ABSTRACTG protein-coupled receptors are the largest and pharmacologically most important receptor family and are involved in the regulation of most cell functions. Most of them reside exclusively at the cell surface, from where they signal via heterotrimeric G proteins to control the production of second messengers such as cAMP and IP3 as well as the activity of several ion channels. However, they may also internalize upon agonist stimulation or constitutively reside in various intracellular locations. Recent evidence...
Source: Annual Review of Pharmacology and Toxicology - September 8, 2023 Category: Drugs & Pharmacology Authors: Martin J Lohse Andreas Bock Manuela Zaccolo Source Type: research

Targeting Efferocytosis in Inflammaging
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-032723-110507. Online ahead of print.ABSTRACTRapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, ...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Ivan K H Poon Kodi S Ravichandran Source Type: research

Apathy and Motivation: Biological Basis and Drug Treatment
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-022423-014645. Online ahead of print.ABSTRACTApathy is a disabling syndrome associated with poor functional outcomes that is common across a broad range of neurological and psychiatric conditions. Currently, there are no established therapies specifically for the condition, and safe and effective treatments are urgently needed. Advances in the understanding of motivation and goal-directed behavior in humans and animals have shed light on the cognitive and neurobiological mechanisms contributing to apathy, providing an important foundation for the develo...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Harry Costello Masud Husain Jonathan P Roiser Source Type: research

From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-022123-104147. Online ahead of print.ABSTRACTThalidomide and its derivatives are powerful cancer therapeutics that are among the best-understood molecular glue degraders (MGDs). These drugs selectively reprogram the E3 ubiquitin ligase cereblon (CRBN) to commit target proteins for degradation by the ubiquitin-proteasome system. MGDs create novel recognition interfaces on the surface of the E3 ligase that engage in induced protein-protein interactions with neosubstrates. Molecular insight into their mechanism of action opens exciting opportunities to eng...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Vladas Oleinikovas Pablo Gainza Thomas Ryckmans Bernhard Fasching Nicolas H Thom ä Source Type: research

The Nocebo Effect
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-022723-112425. Online ahead of print.ABSTRACTAdverse nocebo responses can cause harm to patients and interfere with treatment adherence and effects in both clinic practice and clinical trials. Nocebo responses refer to negative outcomes to active medical treatments in clinical trials or practice that cannot be explained by the treatment's pharmacologic effects. Negative expectancies and nocebo effects are less known than placebo responses. Nocebo effects can be triggered by verbal suggestions, prior negative experiences, observation of others experienci...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Luana Colloca Source Type: research