Editorial Material
Cell Biology
Brie Trusiano, Juselyn D. Tupik, Irving C. Allen
Summary: Understanding the role of membrane bound transient receptor potential (TRP) ion channels, specifically TRPM8, is crucial for the management and treatment of hyperinflammatory conditions, including inflammatory bowel disease. TRPM8 plays a significant role in prostate cancer and cold sensing neurons, as well as the release of calcitonin gene-related peptide (CGRP) by sensory neurons.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Maria Pertusa, Jocelyn Solorza, Rodolfo Madrid
Summary: Cold thermoreceptor neurons detect temperature drops through sensitive molecular machinery in their peripheral free nerve endings. The main molecule responsible for this detection is the TRPM8 channel. Dysregulation of TRPM8 activity is linked to various diseases including cold hypersensitivity, migraine, dry-eye disease, overactive bladder, and cancer. A better understanding of TRPM8's activation and modulation mechanisms is necessary for developing targeted treatments. This review summarizes the current knowledge on TRPM8 and highlights the recent advancements in cryo-electron microscopy structures, providing insights for future drug design.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Gianluca Bianchini, Mara Tomassetti, Samuele Lillini, Anna Sirico, Silvia Bovolenta, Lorena Za, Chiara Liberati, Rubina Novelli, Andrea Aramini
Summary: The research team developed two TRPM8 antagonists and optimized their potency and metabolic stability through modulation/replacement of bioisosteric chemical groups. Subsequently, they developed new TRPM8 antagonists suitable for topical treatment of ocular painful conditions, which were able to reduce the behavioral responses induced by topical ocular menthol challenge.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Ying Yin, Feng Zhang, Shasha Feng, Kevin John Butay, Mario J. Borgnia, Wonpil Im, Seok-Yong Lee
Summary: This study reveals the structural basis of TRPM8 activation dependent on ligand and PIP2, shedding light on the chemically induced cool sensation in mammals.
Article
Multidisciplinary Sciences
Michael Pycraft Hughes, Emily J. Kruchek, Andrew D. Beale, Stephen J. Kitcatt, Sara Qureshi, Zachary P. Trott, Oriane Charbonnel, Paul A. Agbaje, Erin A. Henslee, Robert A. Dorey, Rebecca Lewis, Fatima H. Labeed
Summary: The membrane potential V-m plays crucial roles in cell function, influencing extracellular potential and ion composition, which has significant implications for cellular interactions and disease development.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Jiahao He, Bin Fang, Shengzhou Shan, Yun Xie, Chuandong Wang, Yifan Zhang, Xiaoling Zhang, Qingfeng Li
Summary: The study identified that Piezo1 channel is overexpressed in myofibroblasts of hypertrophic scar (HS) tissues and plays a regulatory role in fibroblasts, thus participating in HS formation. Piezo1 activity enhances various cellular biological behaviors in response to mechanical stretch in dermal fibroblasts, including proliferation, motility, and differentiation. Additionally, blocking Piezo1 with GsMTx4 peptide injection protected rats from stretch-induced HS formation, suggesting Piezo1 as a potential therapeutic target for HS.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Chuanman Zhou, Qian Zhou, Xiaohui He, Yunxia He, Xiaoqin Wang, Xiaowei Zhu, Yujia Zhang, Long Ma
Summary: This study investigates the effects of K2P and NALCN on behavior using the nematode Caenorhabditis elegans as a model. It finds that the K2P gene twk-40 can regulate motor behavior in C. elegans, and identifies five other K2P genes that may have similar effects. Additionally, it suggests that some K2P and NALCN may oppositely affect behavior in C. elegans.
Article
Chemistry, Medicinal
Werner Treptow
Summary: Membrane proteins can respond to various ligands under external stimuli, including small low-affinity molecules. Understanding the modulation of protein function by such ligands is challenging due to their multiple degenerate interactions with the protein. A new theoretical model based on the Boltzmann model is proposed, which allows the description of the equilibrium shifts of the protein in the presence of small low-affinity ligands. This model can be compared to experimental data at the atomic level, making it useful for interpreting protein-ligand interactions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Werner Treptow
Summary: Membrane proteins respond to a variety of ligands, including small low-affinity molecules, under an external stimulus. Characterizing the atomic-level interactions between these ligands and membrane proteins at dilute concentrations is challenging. A new theoretical description based on the two-state Boltzmann model is developed to understand the allosteric modulation of membrane proteins in the presence of small low-affinity ligands and external stimuli. This model allows for the interpretation of experimental data at the atomic level.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Xue Wang, Dong Zhang, Baoze Liu, Xin Wu, Xiaofen Jiang, Shoufeng Zhang, Yan Wang, Danpeng Gao, Lina Wang, Haolin Wang, Zongming Huang, Xiangfan Xie, Tao Chen, Zhengguo Xiao, Qiyuan He, Shuang Xiao, Zonglong Zhu, Shangfeng Yang
Summary: This work presents a novel and effective mixed-cation passivation system to synergically passivate various types of traps in wide-bandgap perovskite, resulting in record performance of perovskite/organic tandem solar cells. The improvements include increased open-circuit voltage and fill factor, leading to a record power conversion efficiency. Additionally, the passivation system improves the photo and thermal stability of the solar cells.
ADVANCED MATERIALS
(2023)
Review
Chemistry, Medicinal
Alejandro Plaza-Cayon, Rosario Gonzalez-Muniz, Mercedes Martin-Martinez
Summary: This review compiles known information on specific mutations and activation mechanisms of the cation nonselective channel TRPM8, and explores the mechanism of adaptation to different temperatures. By summarizing important residues and compiling mutants, deletions, and chimeras, the review provides a comprehensive understanding of the function and effects of TRPM8 channels.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Chemistry, Physical
Lili Song, Xiaoyun Zhang, Shifan Zhu, Yixue Xu, Yuqiao Wang
Summary: The weak hydrogen adsorption and slow catalytic kinetics of MoS2 in alkaline solution hinder its performance as a catalyst for hydrogen evolution reaction (HER). This study demonstrates that carbon quantum dots (CQDs) can enhance the proton adsorption of MoS2 by establishing a suitable hydrogen adsorption gradient and promoting hydrogen spillover from CQDs to MoS2. The enhanced hydrogen spillover effect by CQDs activated MoS2 offers new possibilities for the design and preparation of efficient and low-cost catalysts.
Article
Chemistry, Multidisciplinary
Kirill V. Sukhoverkov, Maxime G. Corral, Julie Leroux, Joel Haywood, Philipp Johnen, Trevor Newton, Keith A. Stubbs, Joshua S. Mylne
Summary: By exploiting the evolutionary relationship between Plasmodium falciparum and plants, a novel herbicide compound, MMV1206386, with potency comparable to commercial herbicides and a new mode of action was discovered. Weighted rules were shown to be effective in herbicide discovery programs.
Article
Multidisciplinary Sciences
N. Bart, C. Dangel, P. Zajac, N. Spitzer, J. Ritzmann, M. Schmidt, H. G. Babin, R. Schott, S. R. Valentin, S. Scholz, Y. Wang, R. Uppu, D. Najer, M. C. Loebl, N. Tomm, A. Javadi, N. O. Antoniadis, L. Midolo, K. Mueller, R. J. Warburton, P. Lodahl, A. D. Wieck, J. J. Finley, A. Ludwig
Summary: This study demonstrates the control of nucleation and density modulation of self-assembled quantum dots using conventional molecular beam epitaxy. The method allows for wafer-scale density modulation with tunable periodicity, resulting in high-quality quantum dot structures. The technique is universal and applicable to a wide range of semiconductor material systems, enabling the growth of ultra-low noise quantum dots across an entire wafer.
NATURE COMMUNICATIONS
(2022)
Article
Nanoscience & Nanotechnology
Fu-Chiao Wu, Pei-Rong Li, Bo-Ren Lin, Ren-Jie Wu, Horng-Long Cheng, Wei-Yang Chou
Summary: This study explores the light-induced electrical behavior of OTFTs under UV light irradiation, showing that using specific absorption top layers can improve the light response of devices, with some unexpected behaviors observed.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Pharmacology & Pharmacy
Katharina Held, Vincenzo Davide Aloi, Ana Cristina Nogueira Freitas, Annelies Janssens, Andrei Segal, Julia Przibilla, Stephan Ernst Philipp, Yu Tian Wang, Thomas Voets, Joris Vriens
Summary: This study compares the pharmacological properties of different splice variants of TRPM3, demonstrating that the length of the pore-forming loop in the alternative splicing region defines the channel's activation by specific compounds.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Dorien Bamps, Joris Vriens, Jan de Hoon, Thomas Voets
Summary: Chronic pain treatment poses a challenge due to limited efficacy and abuse potential. Research on mechanisms underlying chronic pain states offers opportunities for novel interventions, with TRP channels representing innovative targets for addressing pain sensation at the root.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Letter
Allergy
Wout Backaert, Brecht Steelant, Mark Jorissen, Lukas Van Oudenhove, Karel Talavera, Peter W. Hellings, Laura Van Gerven
Editorial Material
Cell Biology
Katharina Held, Paul Lambrechts, Thomas Voets, Geert Bultynck
Article
Multidisciplinary Sciences
Jan Franken, Helene De Bruyn, Roma Rietjens, Andrei Segal, Dirk De Ridder, Wouter Everaerts, Thomas Voets, Greetje Vande Velde
Summary: Videocystometry is a powerful tool for studying bladder function in animal models, allowing for quantitative analysis of voiding efficiency, urethral flow, vesicoureteral reflux, and the relation between intravesical pressure and flow. It has broad applications in elucidating bladder control mechanisms and developing drugs for LUTd.
Review
Allergy
Enrique Velasco, Miguel Delicado-Miralles, Peter W. Hellings, Juana Gallar, Laura Van Gerven, Karel Talavera
Summary: Nasal hyperreactivity is a key feature in upper airway diseases, and can result from impaired barrier function, hypersensitivity to stimuli, and potentiation of efferent systems. The molecular mechanisms underlying hyperreactivity are not yet fully understood, but further research may offer new insights into therapeutics.
Review
Biochemistry & Molecular Biology
Robbe Naert, Alejandro Lopez-Requena, Karel Talavera
Summary: TRPA1 channel, known for its role in nociceptive neurons, is also expressed in immune cells. While detected in various immune cells, functional measurements remain limited. The channel has been linked to multiple diseases in immune cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Brett Boonen, Justyna B. Startek, Alina Milici, Alejandro Lopez-Requena, Melissa Beelen, Patrick Callaerts, Karel Talavera
Summary: The study found that all four isoforms of TRPA1 channels in Drosophila are activated by citronellal and menthol, with dTRPA1(B) being the least sensitive. The normal avoidance behavior of Drosophila towards these compounds requires dTrpA1. This research sheds light on the physiological roles and chemical sensitivity of TRPA1 channels for further studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Helene De Bruyn, Nikky Corthout, Sebastian Munck, Wouter Everaerts, Thomas Voets
Summary: Understanding the lower urinary tract (LUT) is crucial for developing novel therapies for LUT disorders. We developed a videocystometry technique to accurately monitor the LUT in rodents, but it had limitations in awake and freely moving animals. To overcome this, we used machine learning to automatically analyze bladder filling and voiding cycles in behaving mice. Our findings revealed the effects of anesthesia on urethral relaxation and voiding duration, as well as the decreased bladder capacity after surgical implantation of a catheter. This approach provides a paradigm for noninvasive, in vivo monitoring of hollow organs in behaving animals and highlights the limitations of current standard techniques for studying the LUT in mice.
Article
Biology
Lydie Burglen, Evelien Van Hoeymissen, Leila Qebibo, Magalie Barth, Newell Belnap, Felix Boschann, Christel Depienne, Katrien De Clercq, Andrew G. L. Douglas, Mark P. Fitzgerald, Nicola Foulds, Catherine Garel, Ingo Helbig, Katharina Held, Denise Horn, Annelies Janssen, Angela M. Kaindl, Vinodh Narayanan, Christina Prager, Mailys Rupin-Mas, Alexandra Afenjar, Siyuan Zhao, Vincent Th Ramaekers, Sarah M. Ruggiero, Simon Thomas, Stephanie Valence, Lionel Van Maldergem, Tibor Rohacs, Diana Rodriguez, David Dyment, Thomas Voets, Joris Vriens
Summary: TRPM3 is a plasma membrane cation channel that is sensitive to temperature and neurosteroids and is expressed in various types of cells. Rare variants in TRPM3 have been found in individuals with developmental and epileptic encephalopathy, but the connection between TRPM3 activity and neurological disorders is not well understood. In this study, we identified additional heterozygous missense variants in TRPM3 in 10 patients with a range of neurodevelopmental symptoms. These variants cause a gain-of-function phenotype, leading to increased channel activity and altered calcium levels in cells. Treatment with the TRPM3 antagonist primidone reduced the increased channel activity, suggesting that TRPM3 antagonists could be a potential therapy for these disorders.
Article
Pharmacology & Pharmacy
Jan Daniluk, Thomas Voets
Summary: TRPV1 antagonists have pH-dependent effects on channel inhibition, but their modality selectivity is not strict. The antagonistic efficacy of TRPV1 antagonists is limited at acidic pH, which may restrict their analgesic efficacy in injured tissues.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Clinical Neurology
Lena-Luise Becker, Denise Horn, Felix Boschann, Evelien Van Hoeymissen, Thomas Voets, Joris Vriens, Christine Prager, Angela M. Kaindl
Summary: DEE-SWAS is an age-dependent disease that causes cognitive decline. This study reports on two children with DEE-SWAS and developmental delay/regression, who had missense variants in the TRPM3 gene. Treatment with primidone improved their developmental regression, psychomotor development, and eliminated CSWS.
Article
Pharmacology & Pharmacy
Noemie Luyts, Jan Daniluk, Ana Cristina Nogueira Freitas, Bahar Bazeli, Annelies Janssens, Marie Mulier, Wouter Everaerts, Thomas Voets
Summary: In this study, the effect of Phenazopyridine (PAP) on pain-related Transient Receptor Potential (TRP) channels was investigated. The results showed that PAP can rapidly and reversibly inhibit the cold and menthol sensitivity of TRPM8 channels. This suggests that the inhibition of TRPM8 may be the mechanism underlying the analgesic activity of PAP.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
