Review
Biochemistry & Molecular Biology
Kinji Ohno, Bisei Ohkawara, Xin-Ming Shen, Duygu Selcen, Andrew G. Engel
Summary: Congenital myasthenic syndromes (CMS) are a group of heterogeneous disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic variants in genes expressed at the neuromuscular junction (NMJ). A total of 35 genes have been reported in CMS, which can be classified into 14 groups based on the pathomechanical, clinical, and therapeutic features of CMS patients. Diagnosing CMS requires measurement of compound muscle action potentials elicited by repetitive nerve stimulation, and accurate diagnosis always requires genetic studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Yan Tang, Haihong Zong, Hyokjoon Kwon, Yunping Qiu, Jacob B. Pessin, Licheng Wu, Katherine A. Buddo, Ilya Boykov, Cameron A. Schmidt, Chien-Te Lin, P. Darrell Neufer, Gary J. Schwartz, Irwin J. Kurland, Jeffrey E. Pessin
Summary: Cholinergic and sympathetic counter-regulatory networks regulate various physiological functions through increased glycolysis, including blood pressure, heart rate, and energy balance. Increased cholinergic signaling has metabolic benefits, particularly in increasing energy expenditure and heat production during cold exposure.
Article
Clinical Neurology
Marina Spoerrer, Delf Kah, Richard C. Gerum, Barbara Reischl, Danyil Huraskin, Claire A. Dessalles, Werner Schneider, Wolfgang H. Goldmann, Harald Herrmann, Ingo Thievessen, Christoph S. Clemen, Oliver Friedrich, Said Hashemolhosseini, Rolf Schroeder, Ben Fabry
Summary: The study investigated the impact of a desmin mutation on the function of in vitro-engineered muscle micro-tissues, finding that mutated tissues exhibited spontaneous contractions, higher contractile forces, and faster recovery compared to wild-type tissues. Mutated tissues disintegrated within one week of culture, and showed partial or complete rupture under tetanic stimulation, while wild-type tissues remained intact. The results suggest that mechanical damage from high-intensity muscle contractions may exacerbate the degeneration process in desminopathies, highlighting the potential of micro-tissues for studying myocyte organization and disease mechanisms.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Food Science & Technology
Tam M. Huynh, Wayne C. Hodgson, Geoffrey K. Isbister, Anjana Silva
Summary: The study found that commercial antivenoms can partially reverse post-synaptic neurotoxicity induced by snake venom, with varying degrees and rates. The observations suggest that commercial antivenoms are likely to actively reverse established alpha-neurotoxin-mediated neuromuscular paralysis in snake envenoming and exhibit cross-neutralisation with different antivenoms.
Article
Clinical Neurology
Eduardo P. Estephan, Antonio A. Zambon, Rachel Thompson, Kiran Polavarapu, Danny Jomaa, Ana Topf, Paulo V. P. Helito, Carlos O. Heise, Cristiane A. M. Moreno, Andre M. S. Silva, Joao A. Kouyoumdjian, Maria da Penha Morita, Umbertina C. Reed, Hanns Lochmuller, Edmar Zanoteli
Summary: This study focused on phenotype features and the correlation with molecular diagnosis of congenital myasthenic syndromes (CMS) patients, showing a higher chance of confirmed molecular diagnosis in group A and a lower chance in group C. It was found that some individual clinical features, alterations on biopsy, and electrophysiology can enhance the specificity for CMS diagnosis.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
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
Biochemistry & Molecular Biology
Asako Saito, Shigeo Matsui, Ayaka Chino, Shota Sato, Nobuaki Takeshita
Summary: In this study, a novel skeletal muscle-type nicotinic acetylcholine receptor (m-nAChR) positive allosteric modulator (PAM), AS3580239, was identified and found to enhance muscle contraction and improve neurotransmission. These findings suggest that m-nAChR PAMs could be a promising therapeutic approach for neuromuscular diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yun Liu, Weichun Lin
Summary: The study found that mutations in the Acta1 gene in the muscle can lead to morphological and functional defects in the neuromuscular junction (NMJ).
HUMAN MOLECULAR GENETICS
(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
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
Geriatrics & Gerontology
Jedd Pratt, Giuseppe De Vito, Marco Narici, Ricardo Segurado, Ludmilla Pessanha, Jackie Dolan, Judith Conroy, Colin Boreham
Summary: This study confirms the relevance of plasma CAF as a biomarker for sarcopenia, showing significant associations with muscle mass and elevated levels in sarcopenic individuals. Gender differences were observed, with males showing elevated CAF levels in low grip strength or low ALM, while only low ALM in females had significantly raised CAF concentrations compared to healthy controls.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Neurosciences
Maria H. H. Balch, Hallie Harris, Deepti Chugh, Surya Gnyawali, Cameron Rink, Shahid M. Nimjee, W. David Arnold
Summary: Research shows that ischemic stroke leads to neuromuscular junction pathology, including increased polyaxonal innervation. Robot-Assisted Mechanical massage Therapy can improve post-stroke neuromuscular junction alterations.
EXPERIMENTAL NEUROLOGY
(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
Physiology
Tatjana Straka, Charlotte Schroder, Andreas Roos, Laxmikanth Kollipara, Albert Sickmann, Marion Patrick Ivey Williams, Mathias Hafner, Muzamil Majid Khan, Rudiger Rudolf
Summary: Recent studies have shown that neuromuscular junctions are co-innervated by sympathetic neurons, which are crucial for maintaining the morphology and function of neuromuscular junctions. Research using various approaches has revealed that sympathetic innervation plays a significant role in muscle and neuromuscular junction homeostasis, leading to changes such as reduced fiber diameters and enhanced acetylcholine receptor turnover. These findings suggest an upregulation of endocytic and autophagic trafficking at the whole muscle level and at the neuromuscular junction.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Neurosciences
Elana Molotsky, Yuhong Liu, Andrew P. Lieberman, Diane E. Merry
Summary: This study examines the relationship between neuromuscular junction (NMJ) pathology and vulnerability of fast-twitch motor units in spinal and bulbar muscular atrophy (SBMA) mouse models. The research reveals significantly increased NMJ and myofiber pathology in fast-twitch motor units, along with metabolic dysregulation and myofiber atrophy.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Letter
Clinical Neurology
H. Argente-Escrig, D. Schultheis, L. Kamm, M. Schowalter, C. Thiel, M. Tuerk, C. S. Clemen, N. Muelas, M. J. Castanon, G. Wiche, H. Herrmann, J. J. Vilchez, R. Schroeder
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Martin Rees, Roksana Nikoopour, Atsushi Fukuzawa, Ay Lin Kho, Miguel A. Fernandez-Garcia, Elizabeth Wraige, Istvan Bodi, Charu Deshpande, Oezkan Oezdemir, Hulya-Sevcan Daimagueler, Mark Pfuhl, Mark Holt, Birgit Brandmeier, Sarah Grover, Joel Fluss, Cheryl Longman, Maria Elena Farrugia, Emma Matthews, Michael Hanna, Francesco Muntoni, Anna Sarkozy, Rahul Phadke, Ros Quinlivan, Emily C. Oates, Rolf Schroeder, Christian Thiel, Jens Reimann, Nicol Voermans, Corrie Erasmus, Erik-Jan Kamsteeg, Chaminda Konersman, Carla Grosmann, Shane McKee, Sandya Tirupathi, Steven A. Moore, Ekkehard Wilichowski, Elke Hobbiebrunken, Gabriele Dekomien, Isabelle Richard, Peter Van den Bergh, Cristina Dominguez-Gonzalez, Sebahattin Cirak, Ana Ferreiro, Heinz Jungbluth, Mathias Gautel
Summary: The diagnosis of TTN-related myopathies can be complicated due to overlap with other myopathies and TTN variants in control populations. This study identified key clinical and pathological features that can suggest TTN-related myopathies, and demonstrated the destabilizing nature of missense mutations associated with CMs. These findings suggest a potential therapeutic target for recessive titinopathies.
ACTA NEUROPATHOLOGICA
(2021)
Article
Genetics & Heredity
Katalin L. M. L. Hetzelt, Frank Kerling, Cornelia Kraus, Christophe Rauch, Christian T. Thiel, Martin Winterholler, Andre Reis, Christiane Zweier
Summary: PPP2R5D-related neurodevelopmental disorder (NDD) is a rare genetic disease characterized by developmental delay and intellectual disability. Recent findings suggest that individuals with this disorder may also develop Parkinson's disease in early adulthood. This study expands our understanding of this condition and provides new insights for therapeutic management.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Letter
Genetics & Heredity
Sarah Schuhmann, Heiko Koller, Heinrich Sticht, Cornelia Kraus, Mandy Krumbiegel, Steffen Uebe, Arif B. Ekici, Andre Reis, Christian T. Thiel
Article
Genetics & Heredity
Katalin L. M. L. Hetzelt, Martin Winterholler, Frank Kerling, Christophe Rauch, Arif B. Ekici, Andreas Winterpacht, Georgia Vasileiou, Steffen Uebe, Christian T. Thiel, Cornelia Kraus, Andre Reis, Christiane Zweier
Summary: Cohen-Gibson syndrome is a rare genetic disorder caused by mutations in the EED gene, characterized by overgrowth and intellectual disability. This study identified a new heterozygous missense variant responsible for the syndrome, expanding the clinical spectrum and demonstrating clinical variability among patients.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Clinical Neurology
Christoph S. Clemen, Andreas Schmidt, Lilli Winter, Fabio Canneva, Ilka Wittig, Lore Becker, Roland Coras, Carolin Berwanger, Andreas Hofmann, Britta Eggers, Katrin Marcus, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabe de Angelis, Marcus Kruger, Stephan von Horsten, Ludwig Eichinger, Rolf Schroder
Summary: The study investigated N471D Washc5 knock-in and knock-out mice as models for SPG8. Knock-in mice exhibited mild clinical and laboratory abnormalities, but not a typical SPG8 phenotype. Knock-out mice showing normal WASHC5 levels could not be bred to homozygosity, suggesting essential role of WASHC5 in development.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Environmental Sciences
Patrick Lau, Asa Beijer, Andre Rosenberger, Eckhard Schoenau, Christoph Stephan Clemen, Jochen Zange, Jorn Rittweger
Summary: This study examined the acute and protracted effects of resistive exercise and resistive exercise with whole-body vibration on metabolic markers of bone metabolism. Results showed differences in acute responses between the two exercise modalities, but no significant enhancement of bone turnover was observed after six weeks of training.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Cell Biology
Jana Riehl, Ramesh Rijal, Leonie Nitz, Christoph S. Clemen, Andreas Hofmann, Ludwig Eichinger
Summary: The UBX domain-containing protein 9 (UBXD9) interacts with p97 primarily through its UBX domain, affecting p97's ATPase activity and identifying novel interaction partners, including glutamine synthetase type III and several actin-binding proteins.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Marina Spoerrer, Delf Kah, Richard C. Gerum, Barbara Reischl, Danyil Huraskin, Claire A. Dessalles, Werner Schneider, Wolfgang H. Goldmann, Harald Herrmann, Ingo Thievessen, Christoph S. Clemen, Oliver Friedrich, Said Hashemolhosseini, Rolf Schroeder, Ben Fabry
Summary: The study investigated the impact of a desmin mutation on the function of in vitro-engineered muscle micro-tissues, finding that mutated tissues exhibited spontaneous contractions, higher contractile forces, and faster recovery compared to wild-type tissues. Mutated tissues disintegrated within one week of culture, and showed partial or complete rupture under tetanic stimulation, while wild-type tissues remained intact. The results suggest that mechanical damage from high-intensity muscle contractions may exacerbate the degeneration process in desminopathies, highlighting the potential of micro-tissues for studying myocyte organization and disease mechanisms.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Genetics & Heredity
Melissa Rieger, Matthias Tuerk, Cornelia Kraus, Steffen Uebe, Arif B. Ekici, Mandy Krumbiegel, Cord Huchzermeyer, Andre Reis, Christian Thiel
Summary: Steroid 5 alpha-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare metabolic disease characterized by psychomotor disability and eye malformations. This study reports the case of twins with SRD5A3-CDG and identifies a new variant. The study also uncovers a rare symptom associated with SRD5A3-CDG.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Neurosciences
Jiang Zhu, Sara Pittman, Dhruva Dhavale, Rachel French, Jessica N. Patterson, Mohamed Salman Kaleelurrrahuman, Yuanzi Sun, Jaime Vaquer-Alicea, Gianna Maggiore, Christoph S. Clemen, William J. Buscher, Jan Bieschke, Paul Kotzbauer, Yuna Ayala, Marc I. Diamond, Albert A. Davis, Conrad Weihl
Summary: This study identified the multifunctional AAA ATPase VCP as a suppressor of alpha S and TDP-43 aggregate seeding in cells and neurons. VCP may protect against the spread of pathogenic protein aggregates by facilitating the clearance of damaged lysosomes.
MOLECULAR NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Rakesh Ganji, Joao A. Paulo, Yuecheng Xi, Ian Kline, Jiang Zhu, Christoph S. Clemen, Conrad C. Weihl, John G. Purdy, Steve P. Gygi, Malavika Raman
Summary: The association between the endoplasmic reticulum (ER) and mitochondrial membranes at ER-Mitochondria contact sites (ERMCS) is crucial for lipid synthesis. However, little is known about how these contacts are remodeled and the impact of altered contacts on lipid metabolism. This study reveals that the p97 AAA-ATPase and its adaptor UBXD8 play a role in regulating ERMCS. Loss of p97-UBXD8 leads to increased contacts and changes in lipid metabolism, including membrane lipid saturation. The SREBP1-SCD1 pathway is negatively affected, suggesting the sensitivity of contacts to alterations in membrane lipid composition and saturation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Barbara Elsnicova, Daniela Hornikova, Veronika Tibenska, David Kolar, Tereza Tlapakova, Benjamin Schmid, Markus Mallek, Britta Eggers, Ursula Schloetzer-Schrehardt, Viktoriya Peeva, Carolin Berwanger, Bettina Eberhard, Hacer Durmus, Dorothea Schultheis, Christian Holtzhausen, Karin Schork, Katrin Marcus, Jens Jordan, Thomas Luecke, Peter F. M. van der Ven, Rolf Schroeder, Christoph S. Clemen, Jitka M. Zurmanova
Summary: Desmin mutations cause cardiomyopathies and negatively impact mitochondria. The deficiency of desmin results in impaired oxidative phosphorylation and fatty and amino acid metabolism in cardiac mitochondria. Increased glucose utilization and upregulation of fetal creatine kinase are compensatory mechanisms to maintain myocardial energy supply.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)