On average, humans spend about 26 years of their life sleeping. Increased sleep duration and quality has been linked to reduced disease risk; however, the cellular and molecular underpinnings of sleep remain open questions. It has been known for some time that pharmacological modulation of neurotransmission in the brain can promote either sleep or wakefulness thereby providing some clues about the molecular mechanisms at play. However, the field of sleep research has developed an increasingly detailed understanding of the requisite neuronal circuitry and key neurotransmitter receptor subtypes, suggesting that it may be possible to identify next generation pharmacological interventions to treat sleep disorders within this same space. The aim of this work is to examine the latest physiological and pharmacological findings highlighting the contribution of ligand gated ion channels including the inhibitory GABA and glycine receptors and excitatory nicotinic acetylcholine receptors and glutamate receptors in the sleep-wake cycle regulation. Overall, a better understanding of ligand gated ion channels in sleep will help determine if these highly druggable targets could facilitate a better night's sleep.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bcp.2023.115532 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Logic-Gated DNA Intelligent Nanorobots for Cellular Lysosome Interference and Enhanced Therapeutics.
Angew Chem Int Ed Engl
January 2025
University of Science and Technology of China, Department of Chemistry, 96 JinZhai Road, 230026, Hefei, CHINA.
Environment-recognizing DNA nanodevices have proven promising for cellular manipulation and disease treatment, whereas how to sequentially respond to different cellular microenvironments remains a challenge. To this end, here we elaborate a logic-gated intelligent DNA nanorobot (Gi-DR) for the cascade response to inter- and intra-cellular microenvironments, thereby achieving lysosome-targeted cargo delivery for subcellular interference and tumor treatment with enhanced efficacy. Utilizing G-quadruplexes to respond to high-level K+ in cancer cell surrounding, this Gi-DR nanorobot can activate an aptamer-based transmembrane DNA machine that delivers molecular payloads to cellular lysosome.
View Article and Find Full Text PDFInsight into the Mechanism of d-Glucose Accelerated Exchange in GLUT1 from Molecular Dynamics Simulations.
Biochemistry
January 2025
BHF Centre of Research Excellence, School of Medicine and Life Sciences, King's College London, London SE1 9NH, United Kingdom.
Transmembrane glucose transport, facilitated by glucose transporters (GLUTs), is commonly understood through the simple mobile carrier model (SMCM), which suggests that the central binding site alternates exposure between the inside and outside of the cell, facilitating glucose exchange. An alternative "multisite model" posits that glucose transport is a stochastic diffusion process between ligand-operated gates within the transporter's central channel. This study aims to test these models by conducting atomistic molecular dynamics simulations of multiple glucose molecules docked along the central cleft of GLUT1 at temperatures both above and below the lipid bilayer melting point.
View Article and Find Full Text PDFInvestigation into the effect of phenylalanine gating on anaerobic haem breakdown using the energy landscape approach.
Protein Sci
February 2025
Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
We have recently demonstrated a novel anaerobic NADH-dependent haem breakdown reaction, which is carried out by a range of haemoproteins. The Yersinia enterocolitica protein, HemS, is the focus of further research presented in the current paper. Using conventional experimental methods, bioinformatics, and energy landscape theory (ELT), we provide new insight into the mechanism of the novel breakdown process.
View Article and Find Full Text PDFUsing Protein Painting Mass Spectrometry to Define Ligand Receptor Interaction Sites for Acetylcholine Binding Protein.
Bio Protoc
January 2025
School of Systems Biology, George Mason University, Fairfax, VA, USA.
Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels expressed in nervous and non-nervous system tissue important for memory, movement, and sensory processes. The pharmacological targeting of nAChRs, using small molecules or peptides, is a promising approach for the development of compounds for the treatment of various human diseases including inflammatory and neurogenerative disorders such as Alzheimer's disease. Using the acetylcholine binding protein (Ac-AChBP) as an established structural surrogate for human homopentameric α7 nAChRs, we describe an innovative protein painting mass spectrometry (MS) method that can be used to identify interaction sites for various ligands at the extracellular nAChR site.
View Article and Find Full Text PDFTherapeutic Efficacy of 's Oil and Ethanol Extract in Regulation of the Neuroinflammation, Histopathological Alterations, Oxidative Stress, and Restoring Balance Treg Cells Expressing FoxP3+ in a Rat Model of Epilepsy.
Pharmaceuticals (Basel)
December 2024
Zoology Department, Faculty of Science, Fayoum University, Fayoum 63514, Egypt.
: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!