Review
Biochemistry & Molecular Biology
Maria Isabel G. Lopez Sanchez, Annika Kruger, Dmitrii I. Shiriaev, Yong Liu, Joanna Rorbach
Summary: Mammalian mitochondrial ribosomes synthesize proteins essential for oxidative phosphorylation machinery, and their assembly involves complex processes coordinated by multiple factors. Dysregulation of mitoribosome production is linked to metabolic and neurodegenerative diseases, with mutations in various genes contributing to human pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Baozhen Qi, Shimo Dai, Yu Song, Dongli Shen, Fuhai Li, Lanfang Wei, Chunyu Zhang, Zhenning Nie, Jiaxiong Lin, Lidong Cai, Junbo Ge
Summary: This study investigated the role of Na(V)1.8 in ventricular arrhythmias in the AMI model, finding that blockade of NaV1.8 in ganglionated plexi increased the incidence of ventricular arrhythmias in AMI hearts. The study demonstrates an influence of SCN10A/Na(V)1.8 on the regulation of ventricular arrhythmogenesis via modulating ganglionated plexi activity in the AMI model.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Jennifer R. Deuis, Lotten Ragnarsson, Samuel D. Robinson, Zoltan Dekan, Lerena Chan, Ai-Hua Jin, Poanna Tran, Kirsten L. McMahon, Shengnan Li, John N. Wood, James J. Cox, Glenn F. King, Volker Herzig, Irina Vetter
Summary: A peptide named β-theraphotoxin-Eo1a was discovered from the venom of the Tanzanian black and olive baboon tarantula, which modulates the function of Na(V)1.8 channels. Eo1a increases the peak current of Na(V)1.8 and causes significant shifts in the voltage-dependence of activation and steady-state fast inactivation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Matthew Alsaloum, Julie I. R. Labau, Shujun Liu, Mark Estacion, Peng Zhao, Fadia Dib-Hajj, Stephen G. Waxman
Summary: This study investigated the effects of Na(V)1.8 and Na(V)1.9 currents on the excitability of sensory neurons using dynamic clamp electrophysiology. It found direct relationships between Na(V)1.8 current density and action potential parameters, as well as effects of Na(V)1.9 current density on neuronal membrane potential and rheobase. Additionally, the study explored the simultaneous interplay between Na(V)1.8 and Na(V)1.9 on neuronal excitability.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Keri Martinowich, Debamitra Das, Srinidhi Rao Sripathy, Yishan Mai, Rakaia F. Kenney, Brady J. Maher
Summary: This article proposes a potential therapeutic strategy for PTHS by identifying and normalizing dysregulated target genes to restore neuron function and behavioral abnormalities. The study found that inhibiting Na(v)1.8 in PTHS mouse models is effective at restoring normal brain circuit activity and behavior.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Philipp Bengel, Nataliya Dybkova, Petros Tirilomis, Shakil Ahmad, Nico Hartmann, Belal A. Mohamed, Miriam Celine Krekeler, Wiebke Maurer, Steffen Pabel, Maximilian Trum, Julian Mustroph, Jan Gummert, Hendrik Milting, Stefan Wagner, Senka Ljubojevic-Holzer, Karl Toischer, Lars S. Maier, Gerd Hasenfuss, Katrin Streckfuss-Bomeke, Samuel Sossalla
Summary: The study reveals the critical role of the sodium channel Na(V)1.8 as a downstream target of CaMKII delta c in arrhythmia formation in heart failure. Knock-out experiments demonstrate the contribution of Na(V)1.8 to the formation of late Na+ current (I-NaL) and its interaction with CaMKII delta c in cardiomyocytes from heart failure patients. The inhibition of Na(V)1.8 reduces diastolic SR-Ca2+ leak and mortality in CaMKII-overexpressing heart failure mice, suggesting a potential prognostic and antiarrhythmic strategy.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
S. T. Nevin, N. Lawrence, A. Nicke, R. J. Lewis, D. J. Adams
Summary: The beta 3 subunit specifically regulates the sodium channel Na(v)1.8, potentially impacting chronic pain, with neuropathic pain conditions leading to decreased Na(v)1.8 expression and increased beta 3 subunit levels. This specific modulation occurs through the intracellular domain of the beta 3 subunit for maximal current amplitudes, while the extracellular domain is involved in the effect on recovery kinetics of Na(v)1.8.
Article
Neurosciences
Han-Xiong Bear Zhang, Bruce P. Bean
Summary: Studies have shown that CBD inhibits repetitive action potential firing by directly affecting neuronal excitability, with tight binding to the slow inactivated state of TTX-R channels contributing to this effect.CBD may produce analgesic effects by inhibiting action potential firing through its effects on Na(v)1.8 channels.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Medicine, General & Internal
Jim Jones, Darin J. Correll, Sandra M. Lechner, Ina Jazic, Xiaopeng Miao, David Shaw, Christopher Simard, Jeremiah D. Osteen, Brian Hare, Alina Beaton, Todd Bertoch, Asokumar Buvanendran, Ashraf S. Habib, Lois J. Pizzi, Richard A. Pollak, Scott G. Weiner, Carmen Bozic, Paul Negulescu, Paul F. White
Summary: The oral Na(V)1.8 inhibitor VX-548 has been found to reduce acute pain after abdominoplasty or bunionectomy, with the highest dose showing the most significant reduction. However, lower doses of VX-548 were not significantly different from placebo in terms of pain relief. Adverse events associated with VX-548 were common but mild to moderate in severity.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Neurosciences
Christopher A. Baker, Sidharth Tyagi, Grant P. Higerd-Rusli, Shujun Liu, Peng Zhao, Fadia B. Dib-Hajj, Stephen G. Waxman, Sulayman D. Dib-Hajj
Summary: Patients treated with paclitaxel (PTX) or other antineoplastic agents can develop chemotherapy-induced peripheral neuropathy (CIPN), characterized by numbness and pain. PTX affects the transport of voltage-gated sodium channels in sensory neurons, leading to altered channel trafficking and accumulation at nerve endings. This study found that PTX treatment increased the number and velocity of Na(V)1.8-containing vesicles in axons, suggesting enhanced trafficking. However, there was no increase in Na(V)1.8 current density at the neuronal soma, indicating a differential effect of PTX on trafficking in different cellular compartments.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Cell Biology
Fangyu Zhou, Xin Wang, Lingjun Wang, Xin Sun, Guiqin Tan, Wenwen Wei, Guangbing Zheng, Xiaomin Ma, Dan Tian, Hongsong Yu
Summary: This article reviews the role of genetics, epigenetics, cellular immunology, and gut microbiota in the pathogenic mechanism of Graves' disease, which may lead to the development of novel therapeutic strategies and providing promising therapeutic targets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Genetics & Heredity
Bharati Naik, Sumayyah M. Q. Ahmed, Suparna Laha, Shankar Prasad Das
Summary: Fungi have formed symbiotic relationships with different parts of the human body over time, and certain factors can trigger their transition to a pathogenic state. Host genetics play a crucial role in fungal infection, influencing the recognition between pathogen-associated molecular patterns and host pattern recognition receptor molecules through mutations.
FRONTIERS IN GENETICS
(2021)
Article
Pharmacology & Pharmacy
Kiran George, Diego Lopez-Mateos, Tarek Mohamed Abd El-Aziz, Yucheng Xiao, Jake Kline, Hong Bao, Syed Raza, James D. Stockand, Theodore R. Cummins, Luca Fornelli, Matthew P. Rowe, Vladimir Yarov-Yarovoy, Ashlee H. Rowe
Summary: This study investigates the gating mechanism of voltage-gated sodium channel Na(V)1.8 and identifies a toxin, NaTx36, produced by Arizona bark scorpions, which can inhibit Na(V)1.8 currents and block pain signals. Mutagenesis experiments reveal critical amino acids involved in the inhibitory effects of NaTx36. Computational modeling provides insights into the interaction between the toxin and the channel.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Mine Koprulu, Julia Carrasco-Zanini, Eleanor Wheeler, Sam Lockhart, Nicola D. Kerrison, Nicholas J. Wareham, Maik Pietzner, Claudia Langenberg
Summary: Studying the plasma proteome can help identify new disease processes. In this study, a cis-focused proteogenomic analysis was conducted on plasma proteins from 1,180 individuals, revealing unreported protein quantitative trait loci (pQTL). Shared genetic regulation between pQTLs and health outcomes, improved gene assignment at risk loci, and convergence of phenotypic consequences and gene burden were observed. These findings highlight the value of integrating proteomic and genomic data to identify mediators of metabolic diseases.
Article
Food Science & Technology
Leisiane Pereira Marques, Artur Santos-Miranda, Julliane Vasconcelos Joviano-Santos, Jorge Lucas Teixeira-Fonseca, Fabiana da Silva Alcantara, Jaqueline Oliveira Sarmento, Danilo Roman-Campos
Summary: The fungicide Tebuconazole affects the sodium current of human cardiac sodium channels by reducing its amplitude in a concentration- and voltage-dependent manner. It alters the inactivation properties and recovery kinetics of the current, and enhances closed-state inactivation and use-dependent block. Furthermore, Tebuconazole reduces the increase in late sodium current induced by another insecticide. These findings suggest a new mechanism of cardiotoxicity attributed to Tebuconazole.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Clinical Neurology
Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Margot Geerts, Mike Oakes, Tim J. E. Church, Stephen G. Waxman, Sulayman D. Dib-Hajj, Catharina G. Faber, Ingemar S. J. Merkies
Article
Neurosciences
Ivo Eijkenboom, Maurice Sopacua, Auke B. C. Otten, Monique M. Gerrits, Janneke G. J. Hoeijmakers, Stephen G. Waxman, Raffaella Lombardi, Giuseppe Lauria, Ingemar S. J. Merkies, Hubert J. M. Smeets, Catharina G. Faber, Jo M. Vanoevelen
EXPERIMENTAL NEUROLOGY
(2019)
Article
Clinical Neurology
Ivo Eijkenboom, Maurice Sopacua, Janneke G. J. Hoeijmakers, Bianca T. A. de Greef, Patrick Lindsey, Rowida Almomani, Margherita Marchi, Jo Vanoevelen, Hubertus J. M. Smeets, Stephen G. Waxman, Giuseppe Lauria, Ingemar S. J. Merkies, Catharina G. Faber, Monique M. Gerrits
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2019)
Article
Neurosciences
Malgorzata A. Mis, yang Yang, Brian S. Tanaka, Karolina Gomis-Perez, Shujun Liu, Fadia Dib-Hajj, Talia Adi, Rolando Garcia-Milian, Betsy R. Schulman, Sulayman D. Dib-Hajj, Stephen G. Waxman
JOURNAL OF NEUROSCIENCE
(2019)
Review
Pediatrics
Luke Arthur, Kirsty Keen, Madeleine Verriotis, Judy Peters, Alison Kelly, Richard F. Howard, Sulayman D. Dib-Hajj, Stephen G. Waxman, Suellen M. Walker
JOURNAL OF PEDIATRICS
(2019)
Review
Clinical Neurology
Maurice Sopacua, Janneke G. J. Hoeijmakers, Ingemar S. J. Merkies, Giuseppe Lauria, Stephen G. Waxman, Catharina G. Faber
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2019)
Editorial Material
Neurosciences
Stephen G. Waxman, Sulayman D. Dib-Hajj
Article
Neurosciences
Mathilde R. Israel, Brian S. Tanaka, Joel Castro, Panumart Thongyoo, Samuel D. Robinson, Peng Zhao, Jennifer R. Deuis, David J. Craik, Thomas Durek, Stuart M. Brierley, Stephen G. Waxman, Sulayman D. Dib-Hajj, Irina Vetter
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Multidisciplinary Sciences
Zvonimir Vrselja, Stefano G. Daniele, John Silbereis, Francesca Talpo, Yury M. Morozov, Andre M. M. Sousa, Brian S. Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur, Zhen W. Zhuang, Zhao Liu, Rafeed Alkawadri, Albert J. Sinusas, Stephen R. Latham, Stephen G. Waxman, Nenad Sestan
Editorial Material
Anesthesiology
Stephen G. Waxman
Review
Anesthesiology
Stephen G. Waxman
Review
Physiology
David L. Bennett, Alex J. Clark, Jianying Huang, Stephen G. Waxman, Sulayman D. Dib-Hajj
PHYSIOLOGICAL REVIEWS
(2019)
Article
Neurosciences
Jianying Huang, Mark Estacion, Peng Zhao, Fadia B. Dib-Hajj, Betsy Schulman, Angela Abicht, Ingo Kurth, Knut Brockmann, Stephen G. Waxman, Sulayman D. Dib-Hajj
FRONTIERS IN NEUROSCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Milena Sleczkowska, Rowida Almomani, Margherita Marchi, Erika Salvi, Bianca T. A. de Greef, Maurice Sopacua, Janneke G. J. Hoeijmakers, Patrick Lindsey, Stephen G. Waxman, Giuseppe Lauria, Catharina G. Faber, Hubert J. M. Smeets, Monique M. Gerrits
Summary: This study assessed the role of fifteen ion channel genes in neuropathic pain. Variants in ion channel genes were identified in SFN patients, with TRP genes being the most frequent. Patients with these variants reported more severe pain. This study provides promising gene candidates for future research on neuropathic pain etiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Rowida Almomani, Maurice Sopacua, Margherita Marchi, Milena Sleczkowska, Patrick Lindsey, Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Erika Salvi, Ingemar S. J. Merkies, Maryam A. Ferdousi, Rayaz Malik, Dan Ziegler, Kasper W. J. Derks, Gidon Boenhof, Filippo Martinelli-Boneschi, Daniele Cazzato, Raffaella Lombardi, Sulayman G. Dib-Hajj, Stephen Waxman, Hubert J. M. M. Smeets, Monique G. Gerrits, Catharina Faber, Giuseppe Lauria
Summary: Rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification can provide better understanding of the genetic variability in patients with painful and painless neuropathy, leading to improved risk stratification and personalized pain treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)