Article
Biochemistry & Molecular Biology
Fabian Dorninger, Attila Kiss, Peter Rothauer, Alexander Stiglbauer-Tscholakoff, Stefan Kummer, Wedad Fallatah, Mireia Perera-Gonzalez, Ouafa Hamza, Theresa Koenig, Michael B. Bober, Tiscar Cavalle-Garrido, Nancy E. Braverman, Sonja Forss-Petter, Christian Pifl, Jan Bauer, Reginald E. Bittner, Thomas H. Helbich, Bruno K. Podesser, Hannes Todt, Johannes Berger
Summary: The deficiency in ether lipids can cause severe symptoms in humans and the mouse model has been used to study the pathophysiology of the disease. However, the exact role of ether lipids in the cardiac tissue is still unknown. This study found that ether lipid deficiency can lead to cardiac abnormalities in both mice and human patients, but the manifestations are heterogeneous and differ between the two.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Hyemin Lee, Li Zhuang, Boyi Gan
Summary: Recent studies have highlighted the critical role of ether-linked phospholipids in providing polyunsaturated fatty acid-containing phospholipids in ferroptosis, as well as the context-dependent role of TMEM189-mediated vinyl-ether phospholipid synthesis in ferroptosis.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Review
Biochemistry & Molecular Biology
Ellya Bukharaeva, Venera Khuzakhmetova, Svetlana Dmitrieva, Andrei Tsentsevitsky
Summary: Adrenoceptor activators and blockers are commonly used in the clinical treatment of cardiovascular, pulmonary, and neurodegenerative diseases by regulating neurotransmission at the neuromuscular junction. Understanding the molecular mechanisms of these drugs may lead to the development of highly effective and well-tolerated sympathomimetics for treating various neurodegenerative diseases with synaptic defects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Taro Inoue, Bisei Ohkawara, Samira Bushra, Shunsuke Kanbara, Hiroaki Nakashima, Hiroyuki Koshimizu, Hiroyuki Tomita, Mikako Ito, Akio Masuda, Naoki Ishiguro, Shiro Imagama, Kinji Ohno
Summary: Zonisamide enhances agrin-dependent AChR clustering by upregulating the Nrg1/ErbB signaling pathways at the NMJ.
Article
Engineering, Biomedical
Ji Hyun Kim, In Kap Ko, Myung Jae Jeon, Ickhee Kim, Margaret Maria Vanschaayk, Anthony Atala, James J. Yoo
Summary: Efficient innervation is crucial for successful grafting and functional recovery of bioengineered skeletal muscle constructs. In this study, a 3D bioprinted human skeletal muscle construct with pre-formed AChR clusters is developed and shown to accelerate innervation in vivo, leading to functional muscle reconstruction in a rat model of pelvic floor muscle injury.
ACTA BIOMATERIALIA
(2021)
Article
Geriatrics & Gerontology
Li-Kai Tsai, I-Shin Chen, Chi-Chao Chao, Hsueh-Wen Hsueh, Hsin-Hsiung Chen, Yun-Hsin Huang, Rong-Wei Weng, Tzu-Yun Lai, Yi-Chieh Tsai, Yeou-Ping Tsao, Show-Li Chen
Summary: The study revealed the important role of NRIP in the neuromuscular junction, showing its co-localization and interaction with AChR-associated proteins. Anti-NRIP autoantibody was found in patients with myasthenia gravis, potentially exacerbating disease severity.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Review
Biochemistry & Molecular Biology
Bisei Ohkawara, Mikako Ito, Kinji Ohno
Summary: This review focuses on secreted signaling molecules that regulate the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ), including neural agrin, Lrp4, MuSK, Rspo2, Fgf18, and Ctgf. These molecules play crucial roles in ensuring efficient signal transduction at the NMJ.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Hui -Lam Rachel Kwan, Zora Chui-Kuen Chan, Xinyi Bi, Justyna Kutkowska, Tomasz J. Proszynski, Chi Bun Chan, Chi Wai Lee
Summary: Junctional folds are unique membrane specializations that develop during the postnatal maturation of vertebrate neuromuscular junctions (NMJs). This study demonstrates the progressive development of membrane infoldings via nerve-independent, caveolin-3-dependent mechanisms and identifies their roles in AChR trafficking and redistribution during the structural maturation of NMJs.
Article
Biochemistry & Molecular Biology
Guzalia F. Zakirjanova, Arthur R. Giniatullin, Chulpan R. Gafurova, Artem I. Malomouzh, Nikita S. Fedorov, Arthur N. Khaziev, Andrei N. Tsentsevitsky, Alexey M. Petrov
Summary: This study investigates the effects of enzymatic cholesterol oxidation on neuromuscular transmission in mice diaphragms. The results show that cholesterol oxidation disrupts lipid-ordering in synaptic membranes, decreases synaptic delay and exocytosis probability, enhances neurotransmitter and dye release, and inhibits extracellular acetylcholine accumulation. Additionally, cholesterol oxidation affects the mode of exocytosis and may be related to lipid raft disruption.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Nikita Zhilyakov, Arsenii Arkhipov, Artem Malomouzh, Dmitry Samigullin
Summary: Cholinergic neurotransmission plays a key role in both the peripheral and central nervous systems, but certain aspects of its regulation remain unclear. Studies suggest that nicotine can decrease ACh release by enhancing calcium influx through Ca(v)1 channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Manami Yamashita, Yoshihiro Egashira, Shuntaro Nakamura, Souhei Sakata, Fumihito Ono
Summary: This study found that pancuronium, a non-depolarizing muscle relaxant, inhibits fast muscle fibers at a lower concentration compared to slow muscle fibers in zebrafish. The researchers also discovered that this difference is due to the different composition of acetylcholine receptors between slow and fast muscle fibers in the neuromuscular junction of zebrafish.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Neurosciences
Matheus P. S. Magalhaes-Gomes, Wallace Camargos, Priscila A. C. Valadao, Rubens S. Garcias, Hermann A. Rodrigues, Jessica N. Andrade, Vanessa P. Teixeira, Ligia A. Naves, Walter L. G. Cavalcante, Marcia Gallaci, Silvia Guatimosim, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim
Summary: Increased VAChT expression leads to higher levels of ACh release, but may have detrimental effects on the structure and function of the neuromuscular system, including impaired synaptic vesicle cycle and structural alterations of NMJs.
Review
Cell Biology
Mayrene Horta Remedios, Weisheng Liang, Lucas N. Gonzalez, Victoria Li, Vanina G. Da Ros, Debora J. Cohen, Vanina Zaremberg
Summary: Sperm lack most membranous organelles and contain abundant ether glycerolipids, including plasmalogens, platelet activating factor, GPI-anchors, and seminolipid. These lipids play important roles in sperm function and performance, making them potential fertility markers and therapeutic targets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Sydney V. Doss, Sebastien Barbat-Artigas, Mikayla Lopes, Bhola Shankar Pradhan, Tomasz J. Proszynski, Richard Robitaille, Gregorio Valdez
Summary: Lynx1 is expressed in skeletal muscles and concentrates at NMJs. It interacts with muscle-specific nAChR subunits and affects the response of skeletal muscles to cholinergic transmission and their contractile properties. Loss of Lynx1 has a minor role in the structural development of NMJs and may primarily function to maintain the structure and function of adult and aging NMJs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Ryan J. Durbin, Dante J. Heredia, Thomas W. Gould, Robert B. Renden
Summary: Neurotransmission is influenced by extracellular pH. Alkalization enhances transmitter release and receptor activation, while acidification inhibits these processes and can activate acid-sensitive conductances in the synaptic cleft. The direction of change differs across synapse types. At the mammalian neuromuscular junction (NMJ), the direction and magnitude of pH transients in the synaptic cleft during transmission remain unclear. In this study, researchers investigated the extracellular pH transients at the cholinergic synapse of the mouse NMJ under near physiological conditions and identified their sources. They found that activity-induced intracellular Ca2+ release in the muscle plays a role in cleft alkalization, whereas PMCA inhibition decreases alkalization. This suggests that cholinergic synapses at the mouse NMJ typically alkalize due to cytosolic Ca2+ liberation during activity, unless under highly strenuous conditions where acidification predominates.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Cell Biology
Fabian Dorninger, Ernst R. Werner, Johannes Berger, Katrin Watschinger
Summary: Due to their unique chemical structure, plasmalogens exhibit distinct biological features and require specialized pathways for biosynthesis and metabolism. Despite some progress, many questions about the regulation of plasmalogen metabolism and their distribution in mammals remain unanswered. This article summarizes current evidence on the regulation of enzymes involved in plasmalogen biosynthesis and degradation, as well as the turnover of plasmalogens, with a focus on plasmalogen traffic in mammals.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Isabelle Weinhofer, Agnieszka Buda, Markus Kunze, Zsofia Palfi, Matthaus Traunfellner, Sarah Hesse, Andrea Villoria-Gonzalez, Jorg Hofmann, Simon Hametner, Gunther Regelsberger, Ann B. Moser, Florian Eichler, Stephan Kemp, Jan Bauer, Joern-Sven Kuehl, Sonja Forss-Petter, Johannes Berger
Summary: The study highlights the importance of ABCD1 in viral infection and host defense, using Epstein-Barr virus (EBV) infection of human B cells, which could be applicable to other herpes- and coronaviruses.
COMMUNICATIONS BIOLOGY
(2022)
Article
Neurosciences
Ernst R. Werner, Danielle Swinkels, Viktorija Juric, Fabian Dorninger, Myriam Baes, Markus A. Keller, Johannes Berger, Katrin Watschinger
Summary: Based on the findings from mouse experiments, the dysfunction of peroxisomes in the liver does not affect the levels of plasmalogens in plasma and tissues. Instead, there is an increase in plasmenylcholine species in the liver. Therefore, this study does not support the hypothesis that hepatocytes supply plasmalogens to tissues.
BRAIN RESEARCH BULLETIN
(2023)
Article
Biochemistry & Molecular Biology
Fabian Dorninger, Attila Kiss, Peter Rothauer, Alexander Stiglbauer-Tscholakoff, Stefan Kummer, Wedad Fallatah, Mireia Perera-Gonzalez, Ouafa Hamza, Theresa Koenig, Michael B. Bober, Tiscar Cavalle-Garrido, Nancy E. Braverman, Sonja Forss-Petter, Christian Pifl, Jan Bauer, Reginald E. Bittner, Thomas H. Helbich, Bruno K. Podesser, Hannes Todt, Johannes Berger
Summary: The deficiency in ether lipids can cause severe symptoms in humans and the mouse model has been used to study the pathophysiology of the disease. However, the exact role of ether lipids in the cardiac tissue is still unknown. This study found that ether lipid deficiency can lead to cardiac abnormalities in both mice and human patients, but the manifestations are heterogeneous and differ between the two.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Bettina Zierfuss, Agnieszka Buda, Andrea Villoria-Gonzalez, Maxime Logist, Jure Fabjan, Patricia Parzer, Claire Battin, Streggi Vandersteene, Inge M. E. Dijkstra, Petra Waidhofer-Soellner, Katharina Grabmeier-Pfistershammer, Peter Steinberger, Stephan Kemp, Sonja Forss-Petter, Johannes Berger, Isabelle Weinhofer
Summary: VLCFA accumulation in X-ALD is associated with macrophage activation through CD36-mediated uptake, leading to pro-inflammatory responses.
JOURNAL OF NEUROINFLAMMATION
(2022)
Editorial Material
Cell Biology
Fabian Dorninger, Johannes Berger, Masanori Honsho
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Jakob Proemer, Cinzia Barresi, Ruth Herbst
Summary: Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development and its activation and signaling are tightly regulated. Recent studies using omics techniques have contributed to a better understanding of MuSK signaling. Impaired MuSK signaling causes muscle weakness, but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling, as well as the role of MuSK in non-muscle tissue.
CELLULAR SIGNALLING
(2023)
Article
Gastroenterology & Hepatology
Suhail Yousuf, Mengjie Qiu, Lena Voith von Voithenberg, Johannes Hulkkonen, Igor Macinkovic, Axel R. Schulz, Domenic Hartmann, Florian Mueller, Margarete Mijatovic, David Ibberson, Karam T. AlHalabi, Jenny Hetzer, Simon Anders, Bernhard Bruene, Henrik E. Mei, Charles D. Imbusch, Benedikt Brors, Mathias Heikenwalder, Matthias M. Gaida, Markus W. Buechler, Andreas Weigert, Thilo Hackert, Susanne Roth
Summary: We used a multi-modal single-cell approach to study the immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). Our findings highlight the exhausted phenotype of CD8 T cells and immunosuppressive features of myeloid cells in PDAC. We also identified immune subsets that diverge from adjacent normal areas and found distinct immunosuppressive subtypes and immune checkpoint composition in PDAC compared to lung adenocarcinoma.
Article
Multidisciplinary Sciences
Roman Bruch, Florian Keller, Moritz Boehland, Mario Vitacolonna, Lukas Klinger, Ruediger Rudolf, Markus Reischl
Summary: The analysis of 3D microscopic cell culture images is crucial for developing new therapeutics. Deep learning algorithms outperform conventional methods but require large amounts of training data. We propose a pipeline that combines simulation and deep learning optimization to generate synthetic 3D cell culture images with known labels.
Article
Neurosciences
Ksenija Martinovic, Jan Bauer, Markus Kunze, Johannes Berger, Sonja Forss-Petter
Summary: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by mutations in the ABCD1 gene. We combined two mouse models to investigate the role of X-ALD oligodendrocytes in demyelination. We found that Abcd1 deficient mice exhibited increased vulnerability in the early demyelinating phase, leading to more severe axonal damage.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Sarah Janice Hoerner, Nathalie Couturier, Mathias Hafner, Ruediger Rudolf
Summary: Neuromuscular cell culture models are essential for studying synapse formation and function, as well as neuromuscular disease mechanisms. Recent advancements in 3D culture technique and hiPSC technology have improved their ability to complement in vivo models. However, the inclusion of Schwann cells in these cultures has been overlooked. This article provides an overview of different types of neuromuscular cocultures and highlights the effects of Schwann cells, along with proposing future research directions.
BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Steffen Manser, Shaun Keck, Mario Vitacolonna, Felix Wuehler, Ruediger Rudolf, Matthias Raedle
Summary: Advancements in imaging techniques and adaptive visualization tools allow researchers to gain detailed insights into cellular organization and function, particularly in the field of biomedical research involving 3D cell cultures. The use of a multi-modal light sheet microscope can provide complementary spatial and molecular information for greater understanding and potential implications for therapy and drug development. The microscope's components specifically target inherent molecule properties like Rayleigh and Stokes Raman scattering, facilitating marker-free imaging and minimizing external influences on samples.
Article
Multidisciplinary Sciences
Michael Neumaier, Sophie Giesler, Volker Ast, Mathis Roemer, Timo-Daniel Voss, Eileen Reinz, Victor Costina, Martin Schmelz, Elina Nuernberg, Stefanie Nittka, Aino-Maija Leppae, Ruediger Rudolf, Andreas Trumpp, Tina Fuchs
Summary: This report introduces a new class of innate immune cells, called VIREMs, which are myeloid cells unrelated to lymphocytes. The researchers found that B-VIREMs, a subtype of VIREMs, have the ability to genetically recombine and express antibody genes, similar to B lymphocytes. They also discovered that B-VIREMs circulate in the blood of healthy individuals and undergo clonal expansion in response to disease stimuli. Live-cell imaging models suggest that B-VIREMs load their own Fc receptors with endogenous antibodies during vesicle transport. The findings suggest that these innate immune cells have important antigen-specific tissue maintenance functions.
Article
Cell Biology
Tobias F. Primke, Rebecca Ingelfinger, Mohammed A. F. Elewa, Igor Macinkovic, Andreas Weigert, Matthias P. Fabritius, Christoph A. Reichel, Angelika Ullrich, Uli Kazmaier, Luisa D. Burgers, Robert Fuerst
Summary: Research has found that depolymerizing microtubule-targeting agents can reduce inflammation by inhibiting the expression of pro-inflammatory molecules and decreasing leukocyte adhesion to endothelial cells. These agents not only affect leukocytes but also significantly decrease the inflammatory response of vascular endothelial cells. The study sets a baseline for further exploration of the anti-inflammatory effects of depolymerizing microtubule-targeting agents.
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)