Article
Cell Biology
Alexander Sonne, Lorenzo Peverelli, Aurelio Hernandez-Lain, Cristina Dominguez-Gonzalez, Jesper L. Andersen, Margherita Milone, Alan H. Beggs, Julien Ochala
Summary: In this study, we investigated the effects of MYH2 truncating mutations on the presence and post-translational modifications of myosin heavy chains, as well as the functionality of myosin molecules. We found that these mutations resulted in the presence of type IIa myosin heavy chains with an additional acetylated lysine in patients, accompanied by increased ATP demand, faster actomyosin kinetics, and reduced muscle fiber force.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Neurosciences
Natasha Ranu, Jenni Laitila, Hannah F. Dugdale, Jennifer Mariano, Justin S. Kolb, Carina Wallgren-Pettersson, Nanna Witting, John Vissing, Juan Jesus Vilchez, Chiara Fiorillo, Edmar Zanoteli, Mari Auranen, Manu Jokela, Giorgio Tasca, Kristl G. Claeys, Nicol C. Voermans, Johanna Palmio, Sanna Huovinen, Maurizio Moggio, Thomas Nyegaard Beck, Aikaterini Kontrogianni-Konstantopoulos, Henk Granzier, Julien Ochala
Summary: Nemaline myopathy (NM) is a common genetic muscle disorder associated with mutations in the NEB gene. This study revealed that the myosin stabilizing state, known as super-relaxed state, is impaired in NM patients, leading to increased energy consumption in resting muscle fibers. Proteomics analysis also showed metabolic changes in a nebulin-deficient mouse model. These findings provide insights into the pathophysiology of NM and suggest potential therapeutic targets for NEB-NM.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Yukun Liu, Dongfang Wang, Tianyu Li, Ligang Xu, Zhanfei Li, Xiangjun Bai, Manli Tang, Yuchang Wang
Summary: Septic myopathy, also known as ICU acquired weakness, is a clinical symptom of sepsis patients, characterized by muscle weakness and muscular atrophy, which affects respiratory and motor systems, reduces quality of life, and even threatens survival. Melatonin, a hormone secreted by the pineal gland, has multiple biological functions such as anti-inflammatory, antioxidant, and mitochondrial protection, and may play a role in the repair and regeneration of skeletal muscle atrophy in septic myopathy. This article critically discusses and reviews the effects of melatonin on sepsis and skeletal muscle depletion based on previous research results.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biology
Wei Wen, Chenchen Sun, Zhanglin Chen, Dong Yang, Zuoqiong Zhou, Xiyang Peng, Changfa Tang
Summary: This study investigated the effect of alcohol on skeletal muscle using a zebrafish model and revealed its molecular mechanism. The results showed that alcohol exposure led to decreased body size, skeletal muscle fiber size, swimming performance, and oxygen consumption in zebrafish. Alcohol also increased the expression of markers for muscle atrophy and autophagy, as well as inflammation and oxidative stress.
Article
Biochemistry & Molecular Biology
Keisuke Hitachi, Yuri Kiyofuji, Hisateru Yamaguchi, Masashi Nakatani, Masafumi Inui, Kunihiro Tsuchida
Summary: This study investigated the effects of the loss of MyHC-IIb and MyHC-IIx on skeletal muscle function using a mouse model. The results showed that the simultaneous loss of IIb and IIx led to severe muscle hypoplasia after 2 weeks of age in mice. Increased expression of other MyHCs was observed in 3-week-old mice, but it was not sufficient to compensate for the loss of IIb and IIx. Aberrant sarcomere structure and altered expression of sarcomere components were also observed. These findings contribute to the understanding of molecular mechanisms underlying skeletal muscle wasting disorders caused by the loss of skeletal muscle MyHCs.
Article
Cell Biology
Koichi Ojima, Masahiro Kigaki, Emi Ichimura, Takahiro Suzuki, Ken Kobayashi, Susumu Muroya, Takanori Nishimura
Summary: The dynamics of different isoforms of myosin in skeletal muscle have been studied using a mouse model expressing fluorescently tagged slow and fast myosin. The results showed that the response to protein turnover disturbance varied between slow and fast myofibers. These findings highlight the importance of studying endogenous myosin dynamics in different muscle fiber types.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Elisabetta Brunello, Lorenzo Marcucci, Malcolm Irving, Luca Fusi
Summary: The contraction of skeletal muscle is initiated by an increase in intracellular calcium concentration, causing a change in the structure of actin-containing thin filaments that allows binding of myosin motors from the thick filaments. The release of folded motors is triggered by thick filament stress, suggesting a positive feedback loop. This study reveals the coordination of thin and thick filament activation mechanisms and the coupling of these mechanisms through positive feedback loops, achieving rapid cooperative activation of skeletal muscle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Lindsey A. Lee, Samantha K. Barrick, Ada E. Buvoli, Jonathan Walklate, W. Tom Stump, Michael Geeves, Michael J. Greenberg, Leslie A. Leinwand
Summary: For a long time, sarcomeric myosin heavy chain proteins were believed to only exist in striated muscles where they function as molecular motors. However, an evolutionarily ancient member of this myosin family, MYH7b, has been found in mammalian nonmuscle tissues and is linked to hereditary hearing loss. The functional effects of mutations in MYH7b were unknown until now. This study investigates the effects of two hearing loss-associated mutations on the motor activity, structural and assembly properties of MYH7b.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Adriana S. Trujillo, Karen H. Hsu, Meera C. Viswanathan, Anthony Cammarato, Sanford I. Bernstein
Summary: The residue R369 of myosin heavy chain plays a critical role in the function of skeletal muscles. Substituting this residue with a histidine mutation reduces actin binding ability and impairs flight and jump abilities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Patrick J. Ferrara, Anthony R. P. Verkerke, J. Alan Maschek, Justin L. Shahtout, Piyarat Siripoksup, Hiroaki Eshima, Jordan M. Johnson, Jonathan J. Petrocelli, Ziad S. Mahmassani, Thomas D. Green, Joseph M. McClung, James E. Cox, Micah J. Drummond, Katsuhiko Funai
Summary: Obesity-induced alterations in skeletal muscle lipidome may contribute to reduced muscle contractile force. A study found a strong positive correlation between lysophosphatidylcholine (lyso-PC) abundance and maximal tetanic force production in mouse skeletal muscle, regulated by lyso-PC acyltransferase 3 (LPCAT3). Overexpression of LPCAT3 led to reduced lyso-PC content in muscles, but also weaker force-generating capacity, particularly under high-fat diet conditions. Further research is needed to explore how LPCAT3 may affect protein turnover and promote myopathy.
Article
Cell Biology
Sarah K. Skinner, Angelo Solania, Dennis W. Wolan, Michael S. Cohen, Terence E. Ryan, Russell T. Hepple
Summary: The study found that mitochondrial permeability transition (MPT) is a novel mechanism of skeletal muscle atrophy, operating through the release of mROS and activation of caspase-3. The experiment demonstrated that inhibiting MPT, mROS, or caspase-3 could prevent muscle atrophy in both chemical-induced and disuse models.
Article
Biochemistry & Molecular Biology
Constanza Caceres-Ayala, Rodrigo G. Mira, Maria Jose Acuna, Enrique Brandan, Waldo Cerpa, Daniela L. Rebolledo
Summary: Binge drinking has negative effects on skeletal muscle function, leading to decreased strength, increased fatigability, muscle atrophy, fibrosis, and inflammation. These effects can persist for at least two weeks after alcohol clearance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Cameron Hill, Elisabetta Brunello, Luca Fusi, Jesus Garcia Ovejero, Malcolm Irving
Summary: In this study, the activation of myosin filaments in muscle contraction was found to be mainly influenced by filament stress. A switch-like change in myosin motor conformation at the start of force development was also observed, along with the involvement of filament zonal dynamics in activation.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biology
Arian Mansur, Remi Joseph, Euri S. Kim, Pierre M. Jean-Beltran, Namrata D. Udeshi, Cadence Pearce, Hanjie Jiang, Reina Iwase, Miroslav P. Milev, Hashem A. Almousa, Elyshia McNamara, Jeffrey Widrick, Claudio Perez, Gianina Ravenscroft, Michael Sacher, Philip A. Cole, Steven A. Carr, Vandana A. Gupta
Summary: Dysfunction of the ubiquitin-proteasome system (UPS) is associated with various human diseases. This study focuses on understanding the regulation of protein turnover during skeletal muscle development and disease progression. By analyzing the KLHL40-regulated ubiquitin-modified proteome in zebrafish, the researchers identified the role of KLHL40 in ER-Golgi anterograde trafficking and its impact on muscle development. The findings suggest that the muscle proteome is finely regulated by ubiquitylation and uncover new disease mechanisms.
Review
Biochemistry & Molecular Biology
Dumitru Constantin-Teodosiu, Despina Constantin
Summary: Muscle fatigue can decrease the capacity of muscles to complete tasks over time, with short-lasting fatigue often caused by overtraining, undertraining, or physical injury, while persistent and severe fatigue may be associated with pathological states or chronic exposure to certain substances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Marta Alonso-Gardon, Xabier Elorza-Vidal, Aida Castellanos, Gina La Sala, Mercedes Armand-Ugon, Alice Gilbert, Chiara Di Pietro, Adria Pla-Casillanis, Francisco Ciruela, Xavier Gasull, Virginia Nunes, Albert Martinez, Uwe Schulte, Martine Cohen-Salmon, Daniela Marazziti, Raul Estevez
Summary: MLC is a vacuolating leukodystrophy primarily caused by mutations in MLC1 or GLIALCAM genes, with the brain GlialCAM interacting proteome involving various proteins related to brain homeostasis regulation, including G protein-coupled receptors.
HUMAN MOLECULAR GENETICS
(2021)
Correction
Genetics & Heredity
Marc Janier, Mohammed Almadjub, Olivier Beuf, Claire Billotey, Radu Bolbos, Laurence Canaple, Emmanuel Chereul, Denis Grenier, Bassem Hiba, Christophe Odet, Jean-Baptiste Langlois, Carole Lartizien, Luc Magnier, Wilfried Ma, Tarik Zouagui, Mark Lathrop, Ivo Gut, Anne Puech, Yann Herault, Veronique Blanquet, Veronique Brault, Jacques Samarut, Denise Aubert, Michela Plateroti, Nadia Rosenthal, Mumna Al Banchaabouchi, Janice Carter, Olga Ermakova, Karin Gale, Jose Gonzalez, Emerald Perlas, Jeanette Rientjes, Annett Spanner, Anne-Cecile Trillat, Glauco Tocchini-Valentini, Silvia Mandillo, Elisabetta Golini, Daniela Marazziti, Giancarlo Deidda, Nicoletta Rossi, Rafaele Matteoni, Marcello Raspa, Ferdinando Scavizzi, Mariano Barbacid, Marivi Victoria Campuzano, Pierre Dubus, Lucia Perez Gallego, Carmen Guerra Gonzalez, Rudi Balling, Ursula Frischmann, Hansjorg Hauser, Andreas Lengeling, Werner Muller, Bastian Pasche, Martin Hrabe de Angelis, Wolfgang Wurst, Koichiro Abe, Johannes Beckers, Dirk H. Busch, Claudia Dalke, Valerie Gailus Durner, Ralf Elvert, Tobias J. Franz, Helmut Fuchs, Jochen Graw, Sabine M. Holter, Thilo Jakob, Svetoslav Kalaydjiev, Magdalena Kallnik, Martina Klempt, Martin Klingenspor, Thomas Klopstock, Christoph Lengger, Leticia Quintanilla Martinez, Vera Pedersen, Oliver Puk, Ilka Schneider, Daniela Vogt Weisenhorn, Sabine Wagner, Eckhard Wolf, Pierre Chambon, Johan Auwerx, Dalila Ali-Hadji, Marie-France Champy, Nelly Frossard, Jean-Jacques Helwig, Manuel Mark, Laurent Monassier, Maria Cristina Antal, Mariette Barthelmebs, Agnes Bloch-Zupan, Andre Constantinesco, Pascal Doll, Lahcen El Fertak, Francoise Gofflot, Laurent Juillard, Wojciech Krezel, Hamid Meziane, Abdel-Mouttalib Ouagazzal, Francoise Pons, Raymond Romand, Mohammed Selloum, Tania Sorg, Marius Teletin, Laurent Vasseur, Olivia Wendling, Philip Avner, Sophie Chantalat, Urban Lendahl, Johannes Wilbertz, Kay Davies, Peter Oliver, Steve Brown, Michael Cheeseman, Emma Coghill, Roger Cox, Liz Bentley, Simon Ferguson, Hilary Gates, Georgios Gkoutos, Eain Green, John Hancock, Tertius Hough, Robert Johnson, Heena Lad, Ann-Marie Mallon, Pat Nolan, Andy Parker, Julie Quarterman, Adrian Smith, Mandy Studley, Aadya Shukla, Hilda Tateossian, Valter Tucci, Joseph Weekes, Ian Jackson, Sally Cross, Duncan Davidson, Alan Hart, Angus Murray, Anton Berns, Marco Breuer, Evert van Garderen, Jos Jonkers, Ji Ying Song, Martin van der Valk, Ludwig Neyses, Elizabeth Cartwright, Delvac Oceandy, Michael Emerson, Walter Wahli, Maria Belen Delgado, Batrice Desvergne, Liliane Michalik, Elodie Bedu, Denis Duboule, Marie Kmita, Jozsef Zakany, Animage, Allan Bradley, Madhuri Warren
Article
Neurosciences
Cinzia Cocola, Valerio Magnaghi, Edoardo Abeni, Paride Pelucchi, Valentina Martino, Laura Vilardo, Eleonora Piscitelli, Arianna Consiglio, Giorgio Grillo, Ettore Mosca, Roberta Gualtierotti, Daniela Mazzaccaro, Gina La Sala, Chiara Di Pietro, Mira Palizban, Sabino Liuni, Giuseppina DePedro, Stefano Morara, Giovanni Nano, James Kehler, Burkhard Greve, Alessio Noghero, Daniela Marazziti, Federico Bussolino, Gianfranco Bellipanni, Igea D'Agnano, Martin Goette, Ileana Zucchi, Rolland Reinbold
Summary: TMEM230 is crucial for glioblastoma cell growth and migration, inducing behaviors similar to vascular mimicry. High levels of TMEM230 expression correlated with poor prognosis in patients, suggesting it as a potential target for treating GBM and angiogenesis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Marzia Massimi, Chiara Di Pietro, Gina La Sala, Rafaele Matteoni
Summary: This article discusses the relationship between vertebrate G protein-coupled receptor 37 and G protein-coupled receptor 37-like 1 proteins and endothelin and bombesin-specific receptors, as well as their relevance to brain and organ pathologies. It also highlights the application of these genes and proteins in human disease modeling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Adria Pla-Casillanis, Laura Ferigle, Marta Alonso-Gardon, Efren Xicoy-Espaulella, Ekaitz Errasti-Murugarren, Daniela Marazziti, Raul Estevez
Summary: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare white matter brain disorder caused by defects in MLC1 or glial cell adhesion molecule (GlialCAM) proteins. The exact function of MLC proteins and the mechanisms by which they regulate ion channels and transporters remain unclear. Recent research has found that interactions with G protein-coupled receptors (GPCRs) play a significant role in the pathophysiology of MLC disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Eugenia Guida, Valentina Tassinari, Ambra Colopi, Federica Todaro, Valeriana Cesarini, Benedetto Jannini, Manuela Pellegrini, Flavia Botti, Gabriele Rossi, Pellegrino Rossi, Emmanuele A. Jannini, Susanna Dolci
Summary: This study found that overactivation of MAPK in fetal germ cells can lead to neoplastic transformation and metastatic behavior.
JOURNAL OF CELL SCIENCE
(2022)
Review
Biology
Valentina Tassinari, Cristina Cerboni, Alessandra Soriani
Summary: ADAR1 mediates immune response modulation by A-to-I editing, preventing the development of autoimmune diseases and cancer. The activity of ADAR1 prevents the recognition of endogenous dsRNA by cellular sensors, avoiding excessive inflammation and IFN-I production.
Article
Biochemistry & Molecular Biology
Chiara Nardin, Abraham Tettey-Matey, Viola Donati, Daniela Marazziti, Chiara Di Pietro, Chiara Peres, Marcello Raspa, Francesco Zonta, Guang Yang, Maryna Gorelik, Serena Singh, Lia Cardarelli, Sachdev S. Sidhu, Fabio Mammano
Summary: This study presents an all-optical assay for measuring ionized calcium uptake, which allows for the tracking of changes in cytosolic calcium concentration. The assay was demonstrated on cells expressing different Cx proteins and showed potential applications in evaluating HC inhibitors and studying HC expression in cells and tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Valeriana Cesarini, Domenico Alessandro Silvestris, Federica Galeano, Valentina Tassinari, Maurizio Martini, Franco Locatelli, Angela Gallo
Summary: In glioblastoma, the level of ADAR2 protein is correlated with patient prognosis. Reducing ADAR2 protein in GBM cells promotes cell proliferation and migration, and changes the cell's growth mode. Multiple RNAs show differential expression and editing upon siADAR2.
Editorial Material
Biochemistry & Molecular Biology
Daniela Marazziti
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Micaela Lucarelli, Serena Camuso, Chiara Di Pietro, Francesco Bruno, Piergiorgio La Rosa, Daniela Marazziti, Maria Teresa Fiorenza, Sonia Canterini
Summary: Niemann-Pick type C1 (NPC1) disease is a lysosomal lipid storage disorder caused by mutations in the NPC1 gene, leading to cholesterol accumulation. The disease is characterized by progressive Purkinje cell degeneration and ataxia. In a mouse model, impaired Sonic hedgehog signaling was found to affect cerebellar morphogenesis, and it is hypothesized that altered BDNF signaling may contribute to cerebellar alterations in NPC1 disease.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Medicine, General & Internal
Chiara Peres, Caterina Sellitto, Chiara Nardin, Sabrina Putti, Tiziana Orsini, Chiara Di Pietro, Daniela Marazziti, Adriana Vitiello, Arianna Calistri, Mara Rigamonti, Ferdinando Scavizzi, Marcello Raspa, Francesco Zonta, Guang Yang, Thomas W. White, Fabio Mammano
Summary: This study used AAVmAb gene transfer to treat a murine model of KID syndrome with a HC blocking antibody, resulting in reduced lesion size and thickness, inhibition of mutant HC activity, and restoration of normal keratin expression. The findings highlight the critical role of increased HC activity in the skin pathology of KID syndrome and the potential of anti-HC mAbs coupled with genetic delivery systems for treating this incurable disease. Inhibition of HC activity could be a promising therapeutic target in KID syndrome.
Article
Oncology
Carlo Girone, Federica Calati, Irene Lo Cigno, Valentina Salvi, Valentina Tassinari, Tiziana Schioppa, Cinzia Borgogna, Ludovica Lospinoso Severini, John Hiscott, Cristina Cerboni, Alessandra Soriani, Daniela Bosisio, Marisa Gariglio
Summary: Activation of RIG-I pathway can effectively treat HPV-associated malignancies by inducing cell apoptosis and enhancing immune cell activity. This strategy has shown promising results in in vitro experiments and mouse models, and holds important implications for clinical treatment and research.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Nutrition & Dietetics
Valentina Tassinari, Antonella Smeriglio, Virgilio Stillittano, Domenico Trombetta, Romano Zilli, Roberta Tassinari, Francesca Maranghi, Giulia Frank, Daniele Marcoccia, Laura Di Renzo
Summary: Endometriosis is a chronic inflammatory disease that is estrogen-dependent and characterized by the presence of extrauterine endometrial tissue, causing pelvic pain and fertility impairment. The exact cause of endometriosis is not fully understood, and conventional therapies have shown effectiveness but with considerable side effects. There is a growing interest in the use of herbal medicine for endometriosis treatment, particularly polyphenols that have anti-endometriotic and anti-inflammatory properties. This review aims to provide an overview of the anti-inflammatory activity of polyphenols in the treatment of endometriosis.
Article
Biotechnology & Applied Microbiology
Valentina Tassinari, Valeriana Cesarini, Sara Tomaselli, Zaira Ianniello, Domenico Alessandro Silvestris, Lavinia Ceci Ginistrelli, Maurizio Martini, Biagio De Angelis, Gabriele De Luca, Lucia Ricci Vitiani, Alessandro Fatica, Franco Locatelli, Angela Gallo
Summary: The study reveals that METTL3 methylates ADAR1 mRNA and increases its protein level, linking m6A and A-to-I editing and promoting glioblastoma growth. ADAR1 plays a crucial role in cancer progression and its knockdown can strongly inhibit glioblastoma growth.