Article
Multidisciplinary Sciences
Jian Huang, Xiao Fan, Xueqin Jin, Sooyeon Jo, Hanxiong Bear Zhang, Akie Fujita, Bruce P. Bean, Nieng Yan
Summary: Cannabidiol (CBD), a nonpsychoactive compound found in cannabis, is effective in treating epilepsy and pain. Researchers have discovered that CBD interacts with Na(v)1.7 channels at sub-micromolar concentrations, providing insights into its therapeutic mechanisms. The identification of binding sites for CBD may lead to the development of improved compounds for medical use.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Xin Wu, Liang Hong
Summary: Calmodulin (CaM) is a small protein that serves as a ubiquitous signal transducer, regulating neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. Mutations in CaM-binding IQ domain can lead to various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Altin Sula, David Hollingworth, Leo C. T. Ng, Megan Larmore, Paul G. DeCaen, B. A. Wallace
Summary: This study identified a previously unidentified receptor site within the NavMs voltage-gated sodium channel, where tamoxifen and its metabolic products bind, inhibiting sodium conductance and potentially leading to the development of new drugs for sodium channelopathies.
Review
Pharmacology & Pharmacy
Goragot Wisedchaisri, Tamer M. Gamal El-Din
Summary: Voltage-gated ion channels are important drug targets for treating human diseases. However, most drugs lack specificity and can cause serious side effects. Recent advancements in imaging techniques have allowed for a better understanding of the structure and function of voltage-gated sodium channels, leading to the development of more precise and low-toxicity drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Michele Pellegrino, Elena Ricci, Rosangela Ceraldi, Alessandra Nigro, Daniela Bonofiglio, Marilena Lanzino, Catia Morelli
Summary: This review highlights the anti-tumor activity of several antiepileptic drugs in breast, prostate, and other cancers. It focuses on their ability to block ion channels and inhibit histone deacetylases, which are well-established tumor markers and molecular targets. The repurposing of already approved drugs as adjuvants in cancer treatment is advantageous due to reduced toxicity and faster clinical approval. The review also discusses the attempt to administer antiepileptic drugs through drug delivery systems to improve their effectiveness and reduce toxicity.
Article
Pharmacology & Pharmacy
Paz Duran, Santiago Loya-Lopez, Dongzhi Ran, Cheng Tang, Aida Calderon-Rivera, Kimberly Gomez, Harrison J. Stratton, Sun Huang, Ya-ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez-Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna
Summary: This study identified argentatin C, a compound derived from the Native American medicinal plant Parthenium incanum, which can block the activity of voltage-gated sodium and calcium channels and has potential as a novel treatment for painful conditions. Experimental results demonstrated that argentatin C decreased ion currents and excitability in sensory neurons and relieved postsurgical pain in a mouse model. Therefore, argentatin C may serve as an alternative therapy for chronic pain management.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Daohua Jiang, Jiangtao Zhang, Zhanyi Xia
Summary: Voltage-gated sodium channels are crucial for the rapid rising-phase of action potentials, and their mutations can lead to various human diseases. Recent studies using cryo-EM structures have provided valuable insights into the mechanism of eukaryotic Na-V channels, offering templates for drug development.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Computer Science, Information Systems
Siguo Wang, Ying He, Zhanheng Chen, Qinhu Zhang
Summary: Deciphering the relationship between transcription factors and DNA sequences is crucial for understanding gene regulation mechanisms. The FCNGRU model proposed in this study combines a fully convolutional neural network with a gated recurrent unit to directly locate transcription factor binding sites. Experiments show that the FCNGRU-double model achieves superior results in predicting TFBSs compared to other methods, demonstrating its effectiveness in computational inference of gene regulation.
IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
(2022)
Review
Pharmacology & Pharmacy
Tamer M. Gamal El-Din, Michael J. Lenaeus
Summary: Voltage-gated sodium channels are crucial proteins involved in action potential initiation and propagation. Recent studies have shown that fenestrations in these channels play important roles in drug binding and gating processes. Understanding the mechanisms of these channels and their associated diseases has significant implications for developing targeted therapeutics.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Elisabetta Tosti, Raffaele Boni, Alessandra Gallo
Summary: Voltage-gated ion channels are membrane proteins that generate electrical signals, and their dysfunction can lead to diseases and pain. Conotoxins, bioactive peptides extracted from marine mollusk venom, have therapeutic effects and can relieve pain, but they may also cause pathological states.
Review
Chemistry, Medicinal
James R. Groome
Summary: This article reviews the study of marine toxins, particularly on their actions on sodium ion channels regulated by transmembrane voltage and neurotransmitters. The focus is on the diverse conotoxin peptides and their potential applications in evolutionary relationships, biological actions, disease therapy, and understanding the structure of ion channels at the atomic level.
Review
Pharmacology & Pharmacy
Phuong T. Nguyen, Vladimir Yarov-Yarovoy
Summary: This review focuses on recent progress, current challenges, and future opportunities in developing sodium channel targeting small molecules and peptides as non-addictive therapeutics for treating pain.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Scott P. Fraser, Rustem Onkal, Margaux Theys, Frank Bosmans, Mustafa B. A. Djamgoz
Summary: The neonatal splice variant of Na(V)1.5 (nNa(V)1.5) in breast and colon cancer cells can be pharmacologically distinguished from the adult counterpart (aNa(V)1.5) by specific antibodies and toxins. This finding may contribute to the development of low molecular weight compounds as non-toxic therapeutic drugs for cancers expressing nNa(V)1.5.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Agronomy
Linlin Yuan, Kun Zhang, Zhenglei Wang, Limin Xian, Kaiyang Liu, Shaoying Wu
Summary: The sodium channel of Drosophila suzukii was cloned and found to have diverse gating properties and RNA editing.
PEST MANAGEMENT SCIENCE
(2023)
Article
Agriculture, Multidisciplinary
Tatsuya Suzuki, Seiji Yamato
Summary: Oxazosulfyl is a novel insecticide that acts by blocking voltage-gated sodium channels in insects, resulting in paralysis. This discovery sheds light on the mode of action of oxazosulfyl as a potential pest control agent in rice fields.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Michael J. Nutt, Yeung Sing Yee, Amanda Buyan, Neil Andrewartha, Ben Corry, George C. T. Yeoh, Scott G. Stewart
Summary: Novel thalidomide derivatives exhibit selective antiproliferative effects on tumorigenic liver progenitor cells, with significant inhibition of LPC migration and reduction of STAT3 phosphorylation, suggesting involvement of the IL-6/JAK/STAT3 axis in their mode of action.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biophysics
Elaine Tao, Ben Corry
Summary: Voltage-gated sodium channels play a crucial role in the electrical activity of nerve and muscle cells, with humans having nine different subtypes. Research indicates that there are four lateral fenestrations within these channels influencing the access of pore blockers. Although there are structural differences among the subtypes, a common pattern in the dimensions of the fenestrations has been observed, with one particular fenestration appearing most favorable for drug access in all subtypes. These findings are significant for the development of pharmacological treatments and the analysis of disease mutations in sodium channel subtypes.
BIOPHYSICAL JOURNAL
(2022)
Review
Biophysics
Yiechang Lin, Amanda Buyan, Ben Corry
Summary: Piezo1 is a mechanically gated ion channel that plays a critical role in converting mechanical stimuli into electrical signals and regulating blood pressure. Recent studies have used cryo-EM structures and computational simulations to investigate the behavior of Piezo1 at an atomistic level. This review summarizes papers that combine computational techniques with experimental approaches to study Piezo1, discussing the limitations of using computational techniques and providing potential directions for future research.
BIOPHYSICAL REVIEWS
(2022)
Article
Chemistry, Physical
Alice J. Hutchinson, Juan F. Torres, Ben Corry
Summary: This study aims to improve the accuracy of MD thermodiffusion models by assessing different water models in recreating thermodiffusion in aqueous NaCl solutions. By comparing the modeled parameters to experimental values, TIP3P-FB is determined to be the best water model.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Grant J. Brown, Pablo F. Canete, Hao Wang, Arti Medhavy, Josiah Bones, Jonathan A. Roco, Yuke He, Yuting Qin, Jean Cappello, Julia I. Ellyard, Katharine Bassett, Qian Shen, Gaetan Burgio, Yaoyuan Zhang, Cynthia Turnbull, Xiangpeng Meng, Phil Wu, Eun Cho, Lisa A. Miosge, T. Daniel Andrews, Matt A. Field, Denis Tvorogov, Angel F. Lopez, Jeffrey J. Babon, Cristina Aparicio Lopez, Africa Gonzalez-Murillo, Daniel Clemente Garulo, Virginia Pascual, Tess Levy, Eric J. Mallack, Daniel G. Calame, Timothy Lotze, James R. Lupski, Huihua Ding, Tomalika R. Ullah, Giles D. Walters, Mark E. Koina, Matthew C. Cook, Nan Shen, Carmen de Lucas Collantes, Ben Corry, Michael P. Gantier, Vicki Athanasopoulos, Carola G. Vinuesa
Summary: Enhanced Toll-like receptor 7 (TLR7) signaling has been associated with human systemic autoimmune disease, but evidence of TLR7 gene variants causing lupus is lacking. In this study, researchers identified a newly described TLR7(Y264H) variant that increased sensing of guanosine and 2',3'-cGMP and was sufficient to cause lupus in mice. Enhanced TLR7 signaling was shown to drive aberrant B cell survival and the accumulation of specific B cell subsets, while deficiency of the downstream adapter protein MyD88 rescued autoimmunity and all phenotypes. The study highlights the importance of TLR7 and guanosine-containing self-ligands in the pathogenesis of lupus and suggests potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Sarah Heckmatt Shafik, Sashika Natasha Richards, Ben Corry, Rowena Elizabeth Martin
Summary: Polymorphisms in the Pfmdr1 and Pfcrt genes alter the susceptibility of the malaria parasite to antimalarial drugs. This study provides insights into the mechanisms by which these genes contribute to drug resistance and explains the phenomenon of collateral drug sensitivity.
Article
Biophysics
Amanda Buyan, D. W. Allender, Ben Corry, M. Schick
Summary: We investigated the effects of Piezo1 protein insertion on the lipid distribution in the plasma membrane. Coarse-grained molecular dynamics simulations revealed that the outer leaflet experienced major changes, with increased cholesterol and decreased phosphatidylcholine and sphingomyelin near Piezo1. The inner leaflet showed slight decreases in cholesterol and phosphatidylethanolamine, slight increase in phosphatidylserine, and significant decrease in phosphatidylcholine near the protein. These findings can be explained by a theoretical model that considers the coupling between actual curvatures and composition-dependent spontaneous curvatures of the leaflets, as well as the influence of cholesterol on the spontaneous curvatures of phospholipids.
BIOPHYSICAL JOURNAL
(2023)
Article
Physiology
Yiechang Lin, Amanda Buyan, Ben Corry
Summary: Piezo2, a membrane protein, interacts with lipids in the membrane and forms long-term interactions with specific lipids at functionally relevant sites. It plays critical roles in sensing mechanical signals and regulating various physiological functions.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Review
Physics, Multidisciplinary
C. Guardiani, F. Cecconi, L. Chiodo, G. Cottone, P. Malgaretti, L. Maragliano, M. L. Barabash, G. Camisasca, M. Ceccarelli, B. Corry, R. Roth, A. Giacomello, B. Roux
Summary: Ion channels act as gates on cellular membranes to ensure selective ion transport, serving as the molecular mechanism for basic biological functions like nerve signal transmission and muscle contraction. Recent computational research on ion channels reviews theoretical advances, simulation approaches, and modeling techniques, including applications to understand permeation, selectivity, and gating mechanisms in biological and model channels.
ADVANCES IN PHYSICS-X
(2022)
Article
Multidisciplinary Sciences
Deyun Qiu, Jinxin V. Pei, James E. O. Rosling, Vandana Thathy, Dongdi Li, Yi Xue, John D. Tanner, Jocelyn Sietsma Penington, Yi Tong Vincent Aw, Jessica Yi Han Aw, Guoyue Xu, Abhai K. Tripathi, Nina F. Gnadig, Tomas Yeo, Kate J. Fairhurst, Barbara H. Stokes, James M. Murithi, Krittikorn Kumpornsin, Heath Hasemer, Adelaide S. M. Dennis, Melanie C. Ridgway, Esther K. Schmitt, Judith Straimer, Anthony T. Papenfuss, Marcus C. S. Lee, Ben Corry, Photini Sinnis, David A. Fidock, Giel G. van Dooren, Kiaran Kirk, Adele M. Lehane
Summary: The G358S mutation in PfATP4 decreases the sensitivity of ATP4 to inhibition by cipargamin and (+)-SJ733, thereby protecting parasites from disruption of Na+ regulation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Anna Robinson, Elaine Tao, Teresa Neeman, Benjamin Kaehler, Ben Corry
Summary: Researchers constructed a homology model of the hSkMNaV1.4 channel to investigate the structural and functional implications of the 59-residue DIS5-S6 linker peptide. The linker peptide, unique to mammalian skeletal muscle sodium ion channels, was found to fold into a compact configuration and may play a critical role in channel gating.
Article
Engineering, Chemical
Zhongjin He, Ben Corry
Summary: The study reveals that under electric fields, the biomimetic nanopore conducts Na+ preferentially and slows down the passage of Ca2+ by selectively binding it to the carboxylate groups. In strong electric fields, a Cl- concentration polarization layer forms on one side of the nanopore, leading to the formation of stable clusters of Cl- and Ca2+ pairs bound at the carboxylate groups, which severely hinders Cl- transport and occasionally suspends the transport of cations. These findings provide design principles and implications for the fabrication of nanoporous graphene membranes for separation applications, such as heavy metal removal from wastewater.
Article
Multidisciplinary Sciences
Zijing Zhou, Xiaonuo Ma, Yiechang Lin, Delfine Cheng, Navid Bavi, Genevieve A. Secker, Jinyuan Vero Li, Vaibhao Janbandhu, Drew L. Sutton, Hamish S. Scott, Mingxi Yao, Richard P. Harvey, Natasha L. Harvey, Ben Corry, Yixiao Zhang, Charles D. Cox
Summary: In this study, the researchers identified MDFIC and MDFI as interacting partners of the PIEZO1/2 channels. These proteins bind to the PIEZO1/2 channels and regulate their inactivation. The researchers also determined the interaction site of MDFIC in the PIEZO1 pore module using cryogenic electron microscopy, providing insights into the gating kinetics of endogenous Piezo channels and potential mechanisms involved in human lymphatic vascular disease.
Article
Biochemistry & Molecular Biology
Eric Sparkes, Elizabeth A. Cairns, Richard C. Kevin, Felcia Lai, Katharina Elisabeth Grafinger, Shuli Chen, Marie H. Deventer, Ross Ellison, Rochelle Boyd, Lewis J. Martin, Iain S. McGregor, Roy R. Gerona, David E. Hibbs, Volker Auwaerter, Michelle Glass, Christophe Stove, Samuel D. Banister
Summary: Synthetic cannabinoid receptor agonists exhibit high affinity and potency for CB1 and CB2 receptors, with different cannabimimetic activities in vivo. Structure-activity relationships (SARs) were identified for binding and functional activities at CB1 and CB2 receptors, providing insights into the pharmacological properties of these compounds.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Biophysics
Amanda Buyan, Aidan A. Whitfield, Ben Corry
Summary: Voltage-gated sodium channels are crucial for encoding and transmitting electrical signals in nerve and muscle cells. Currently, drugs that aim to inhibit these channels lack subtype specificity, with some potential differences observed in how different drugs bind to the channels based on molecular dynamics simulations.
BIOPHYSICAL JOURNAL
(2021)