Review
Biochemistry & Molecular Biology
Kenshiro Fujise, Satoru Noguchi, Tetsuya Takeda
Summary: This review provides an overview of the functions of dynamin 2 and BIN1 in T-tubule biogenesis and discusses how their dysfunction in membrane remodelling leads to CNM pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lucas Bayones, Maria Jose Guerra-Fernandez, Fernando Hinostroza, Ximena Baez-Matus, Jacqueline Vasquez-Navarrete, Luciana Gallo, Sergio Parra, Agustin D. Martinez, Arlek Gonzalez-Jamett, Fernando D. Marengo, Ana M. Cardenas
Summary: Gain-of-function mutations of dynamin-2 result in centronuclear myopathy by impairing exocytosis, disrupting actin filament formation and impacting the plasmalemma expression of functional proteins in skeletal muscle cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Raquel Gomez-Oca, Belinda S. Cowling, Jocelyn Laporte
Summary: Centronuclear myopathies (CNM) are rare congenital disorders characterized by muscle weakness and structural defects caused by mutations in genes encoding proteins involved in membrane remodeling, trafficking, and excitation-contraction coupling. Animal models have confirmed shared pathological anomalies in T-tubule remodeling, organelle mispositioning, and protein homeostasis, supporting the development of common therapeutic targets for CNM forms. Promising preclinical results have led to ongoing clinical trials for CNM treatment, including gene therapy and repurposing of existing drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Jorge Arriagada-Diaz, Carolina Flores-Munoz, Barbara Gomez-Soto, Marjorie Labrana-Allende, Michelle Mattar-Araos, Lorena Prado-Vega, Fernando Hinostroza, Ivana Gajardo, Maria Jose Guerra-Fernandez, Jorge A. Bevilacqua, Ana M. Cardenas, Marc Bitoun, Alvaro O. Ardiles, Arlek M. Gonzalez-Jamett
Summary: This study investigates the effect of the dynamin-2 p.R465W mutation on CNS function and suggests that it disrupts synaptic and cognitive function. The mutation leads to changes in neuronal morphology and impaired excitatory synaptic transmission.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Jorge Arriagada-Diaz, Carolina Flores-Munoz, Barbara Gomez-Soto, Marjorie Labrana-Allende, Michelle Mattar-Araos, Lorena Prado-Vega, Fernando Hinostroza, Ivana Gajardo, Maria Jose Guerra-Fernandez, Jorge A. Bevilacqua, Ana M. Cardenas, Marc Bitoun, Alvaro O. Ardiles, Arlek M. Gonzalez-Jamett
Summary: This study investigated the effect of a mutation in the dynamin-2 gene on central nervous system function. The mutation was found to reduce dendritic arborisation and spine density, as well as impair excitatory synaptic transmission and recognition memory in a mouse model. These findings highlight the role of dynamin-2 in regulating neuronal morphology and synaptic transmission in the hippocampus.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Cell Biology
Suzie Buono, Arnaud Monseur, Alexia Menuet, Anne Robe, Catherine Koch, Jocelyn Laporte, Leen Thielemans, Marion Depla, Belinda S. Cowling
Summary: Generating reliable preclinical data in animal models of disease is crucial for therapy development. In this study, statistical analysis and modeling were conducted to predict disease progression, which was then validated using data from a new colony of mice, demonstrating the reproducibility of disease phenotype. Furthermore, the refined phenotypic parameters were used to test the therapeutic efficacy of Dnm2 targeting, showing a significant improvement in disease progression.
DISEASE MODELS & MECHANISMS
(2022)
Article
Clinical Neurology
Charlotte Gineste, Alix Simon, Marie Braun, David Reiss, Jocelyn Laporte
Summary: The study shows that tamoxifen can improve muscle function and structure in mouse models of BIN1 and DNM2-related centronuclear myopathies, likely by reducing dynamin 2 levels. This suggests the potential repurposing of tamoxifen for the treatment of autosomal forms of centronuclear myopathies.
Review
Clinical Neurology
Kun Huang, Fang-Fang Bi, Huan Yang
Summary: This study estimated the prevalence of congenital myopathy through a systematic review and meta-analysis. The prevalence varied among different subtypes and populations. The overall quality of studies on this disease is generally moderate, emphasizing the need for higher-quality research on orphan diseases.
FRONTIERS IN NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Valentina Maria Lionello, Christine Kretz, Evelina Edelweiss, Corinne Crucifix, Raquel Gomez-Oca, Nadia Messaddeq, Suzie Buono, Pascale Koebel, Xenia Massana Munoz, Nadege Diedhiou, Belinda S. Cowling, Marc Bitoun, Jocelyn Laporte
Summary: This study identifies BIN1 as a potential therapeutic target for dominant centronuclear myopathy linked to DNM2 mutations. By increasing BIN1 expression, muscle atrophy and histopathological features can be improved, and survival can be rescued.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Clinical Neurology
Qi Wang, Meng Yu, Zhiying Xie, Jing Liu, Qingqing Wang, He Lv, Wei Zhang, Yun Yuan, Zhaoxia Wang
Summary: Centronuclear myopathy (CNM) is a group of congenital myopathies characterized by centralized nuclei in muscle fibers. A study in China found DNM2 to be the most common causative gene for CNM in Chinese patients.
NEUROLOGICAL SCIENCES
(2022)
Article
Genetics & Heredity
Stacha F. I. Reumers, Corrie E. Erasmus, Karlijn Bouman, Maartje Pennings, Meyke Schouten, Benno Kusters, Floor A. M. Duijkers, Anneke van Der Kooi, Bregje Jaeger, Corien C. Verschuuren-Bemelmans, Catharina G. Faber, Baziel G. van Engelen, Erik-Jan Kamsteeg, Heinz Jungbluth, Nicol C. Voermans
Summary: Centronuclear myopathy (CNM) is a genetically heterogeneous congenital myopathy characterized by muscle weakness and variable degrees of cardiorespiratory involvement, with severity largely determined by genotype and age of the patient. A retrospective study on 48 CNM patients in the Netherlands revealed diverse clinical features and genetic variations, contributing to trial readiness in the future.
Article
Cell Biology
Karla G. Espinosa, Salma Geissah, Linda Groom, Jonathan Volpatti, Ian C. Scott, Robert T. Dirksen, Mo Zhao, James J. Dowling
Summary: This study reported a new zebrafish model, zebrafish speg-DKO, of centronuclear myopathy (CNM), and demonstrated its ability to accurately recapitulate multiple phenotypes associated with CNM. This model provides a potential platform for investigating disease mechanisms and evaluating potential therapies for CNM.
DISEASE MODELS & MECHANISMS
(2022)
Article
Neurosciences
Tara C. Tassin, Barbara Barylko, Per Niklas Hedde, Yan Chen, Derk D. Binns, Nicholas G. James, Joachim D. Mueller, David M. Jameson, Ronald Taussig, Joseph P. Albanesi
Summary: Mutations in the DNM2 gene are associated with motor disorders affecting nerve and muscle, such as CMT and CNM; CMT and CNM mutations have distinct effects on DNM2 function, suggesting different pathogenic mechanisms and genetic overlap should be re-examined.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Medicine, General & Internal
Narjara Castillo-Ferran, Juan Mario Junco-Rodriguez, Zurina Lestayo-O'Farrill, Maria de los Angeles Robinson-Agramonte, Zoilo Camejo-Leon, Hector Jesus Gomez-Suarez, Mercedes Salinas-Olivares, Evelyn Antiguas-Valdez, Elizabeth Falcon-Lamazares, Dario Siniscalco
Summary: Congenital myopathies (CMs) are a group of diseases characterized by muscle weakness and hypotonia. Centronuclear CM, characterized by centrally located nuclei in muscle fibers, was diagnosed in a 22-year-old male patient with muscle weakness since childhood. Neurogenic patterns were observed in electromyography and neuroconduction studies showed motor nerve involvement. The presence of fibers with central nuclei confirmed the diagnosis of CM. Understanding the pathological findings in CM is important for early treatment.
MEDICINA-LITHUANIA
(2023)
Article
Genetics & Heredity
Kenshiro Fujise, Mariko Okubo, Tadashi Abe, Hiroshi Yamada, Kohji Takei, Ichizo Nishino, Tetsuya Takeda, Satoru Noguchi
Summary: Centronuclear myopathy (CNM) is a group of inherited congenital diseases characterized by clinically progressive muscle weakness and centralized myonuclei, diagnosed through genetic testing and muscle biopsy. A study identified five novel DNM2 variants and used a cell-based assay to establish the pathogenicity of these variants, showing correlations with biochemical features and clinicopathological phenotypes. This approach provides insights into the disease progression of DNM2-associated CNM by combining in cellulo assay with clinical information.
Article
Medicine, Research & Experimental
Delphine Trochet, Bernard Prudhon, Lylia Mekzine, Megane Lemaitre, Maud Beuvin, Laura Julien, Sofia Benkhelifa-Ziyyat, Mai Thao Bui, Norma Romero, Marc Bitoun
Summary: This study demonstrates that mutant-specific RNA interference therapy is effective in rescuing the muscle phenotype in individuals with AD-CNM. The treatment has long-term benefits and prevents the pathological accumulation of mutant protein. The study also highlights the importance of DNM2 protein expression level for muscle function.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Haktan Altinova, Pascal Achenbach, Moniek Palm, Istvan Katona, Emmanuel Hermans, Hans Clusmann, Joachim Weis, Gary Anthony Brook
Summary: Research on using bioengineered scaffolds for spinal cord injury repair showed the formation of scar cells with characteristics of perineurial cells in the spinal cord tissue after scaffold implantation. This change in cellular composition highlights the complexity of scar formation in response to injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Valentina Maria Lionello, Christine Kretz, Evelina Edelweiss, Corinne Crucifix, Raquel Gomez-Oca, Nadia Messaddeq, Suzie Buono, Pascale Koebel, Xenia Massana Munoz, Nadege Diedhiou, Belinda S. Cowling, Marc Bitoun, Jocelyn Laporte
Summary: This study identifies BIN1 as a potential therapeutic target for dominant centronuclear myopathy linked to DNM2 mutations. By increasing BIN1 expression, muscle atrophy and histopathological features can be improved, and survival can be rescued.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Pathology
Danny Jonigk, Christopher Werlein, Till Acker, Martin Aepfelbacher, Kerstin U. Amann, Gustavo Baretton, Peter Barth, Rainer M. Bohle, Andreas Buettner, Reinhard Buettner, Reinhard Dettmeyer, Philip Eichhorn, Sefer Elezkurtaj, Irene Esposito, Katja Evert, Matthias Evert, Falko Fend, Nikolaus Gassler, Stefan Gattenloehner, Markus Glatzel, Heike Goebel, Elise Gradhand, Torsten Hansen, Arndt Hartmann, Axel Heinemann, Frank L. Heppner, Julia Hilsenbeck, David Horst, Jan C. Kamp, Gita Mall, Bruno Maerkl, Benjamin Ondruschka, Jessica Pablik, Susanne Pfefferle, Alexander Quaas, Helena Radbruch, Christoph Roecken, Andreas Rosenwald, Wilfried Roth, Martina Rudelius, Peter Schirmacher, Julia Slotta-Huspenina, Kevin Smith, Linna Sommer, Konrad Stock, Philipp Stroebel, Stephanie Strobl, Ulf Titze, Gregor Weirich, Joachim Weis, Martin Werner, Claudia Wickenhauser, Thorsten Wiech, Peter Wild, Tobias Welte, Saskia von Stillfried, Peter Boor
Summary: This article discusses the importance of autopsies in the context of the COVID-19 pandemic and presents findings from autopsies conducted in German autopsy centers. The study reveals the distribution of SARS-CoV-2 in various organs and tissues, and provides insights into the pathological features and mechanisms of COVID-19. However, the pathological changes in non-respiratory organs remain unclear.
Article
Endocrinology & Metabolism
Joshua Jackson, Lena Wischhof, Enzo Scifo, Anna Pellizzer, Yiru Wang, Antonia Piazzesi, Debora Gentile, Sana Siddig, Miriam Stork, Chris E. Hopkins, Kristian Handler, Joachim Weis, Andreas Roos, Joachim L. Schultze, Pierluigi Nicotera, Dan Ehninger, Daniele Bano
Summary: Mitochondrial retrograde signaling can stimulate organelle biogenesis as a compensatory adaptation to abnormal activity of the oxidative phosphorylation (OXPHOS) system. In this study, the researchers investigated the molecular mechanisms promoting mitochondrial maintenance in energy-deprived cells and identified the sphingosine phosphate lyase SPL-1/SGPL1 and the ATFS-1-target HOPS complex subunit VPS-39/VPS39 as critical lifespan modulators. They also found that VPS39 recruitment to the mitochondria may be a common signature associated with altered OXPHOS system in mouse-derived muscles.
MOLECULAR METABOLISM
(2022)
Article
Clinical Neurology
Andrea Maier, Romina Kapfenberger, Istvan Katona, Joachim Weis, Jorg B. Schulz, Roman Rolke
Summary: In this retrospective analysis of autoimmune autonomic neuropathy (AAN) patients, it was found that neuropathic pain was not as common as sensory loss. Sensory loss was widely distributed, mainly affecting cold and warm detection thresholds and the thermal sensory limen. Serostatus was not a significant predictor of small fiber deficit in AAN.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Deniz Yilmazer-Hanke, Najwa Ouali Alami, Lubin Fang, Sigried Klotz, Gabor G. Kovacs, Helmut Pankratz, Joachim Weis, Istvan Katona, Angelika Scheuerle, Wolfgang J. Streit, Kelly Del Tredici
Summary: The expression of glial markers CHIT1 and CHI3L1 in the human striate cortex and cerebellum after hypoxic-ischemic brain injury was studied. Different expression patterns were found between the two brain regions. CHIT1 and CHI3L1 could be valuable biomarkers for monitoring the outcome of brain injury.
Letter
Neurosciences
Juliane Bremer, Johannes Friemann, Saskia von Stillfried, Peter Boor, Joachim Weis
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Patricia Franzka, Svenja Caren Schueler, Takfarinas Kentache, Robert Storm, Andrea Bock, Istvan Katona, Joachim Weis, Katrin Buder, Christoph Kaether, Christian A. Hubner
Summary: Proteins of the secretory pathway undergo glycosylation in the ER and Golgi apparatus. Mutations in GMPPA can cause AAMR syndrome with various symptoms. Loss of GMPPA leads to Golgi fragmentation, altered protein abundance, reduced furin activity, and increased retention of alpha-DG.
Article
Clinical Neurology
Jorge Arriagada-Diaz, Carolina Flores-Munoz, Barbara Gomez-Soto, Marjorie Labrana-Allende, Michelle Mattar-Araos, Lorena Prado-Vega, Fernando Hinostroza, Ivana Gajardo, Maria Jose Guerra-Fernandez, Jorge A. Bevilacqua, Ana M. Cardenas, Marc Bitoun, Alvaro O. Ardiles, Arlek M. Gonzalez-Jamett
Summary: This study investigates the effect of the dynamin-2 p.R465W mutation on CNS function and suggests that it disrupts synaptic and cognitive function. The mutation leads to changes in neuronal morphology and impaired excitatory synaptic transmission.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Biology
Eline Lemerle, Jeanne Laine, Marion Benoist, Gilles Moulay, Anne Bigot, Clemence Labasse, Angeline Madelaine, Alexis Canette, Perrine Aubin, Jean-Michel Vallat, Norma B. Romero, Marc Bitoun, Vincent Mouly, Isabelle Marty, Bruno Cadot, Laura Picas, Stephane Vassilopoulos
Summary: Excitation-contraction coupling requires a specialized membrane structure called Triad, composed of T-tubule and two sarcoplasmic reticulum terminal cisternae. Bin1 and caveolae are involved in T-tubule formation, and deficiency can lead to muscle weakness and myopathies. Bin1 forms scaffolds for caveolae accumulation and T-tubule formation. Cav3 deficiency causes T-tubule organization defects.
Article
Clinical Neurology
Jorge Arriagada-Diaz, Carolina Flores-Munoz, Barbara Gomez-Soto, Marjorie Labrana-Allende, Michelle Mattar-Araos, Lorena Prado-Vega, Fernando Hinostroza, Ivana Gajardo, Maria Jose Guerra-Fernandez, Jorge A. Bevilacqua, Ana M. Cardenas, Marc Bitoun, Alvaro O. Ardiles, Arlek M. Gonzalez-Jamett
Summary: This study investigated the effect of a mutation in the dynamin-2 gene on central nervous system function. The mutation was found to reduce dendritic arborisation and spine density, as well as impair excitatory synaptic transmission and recognition memory in a mouse model. These findings highlight the role of dynamin-2 in regulating neuronal morphology and synaptic transmission in the hippocampus.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Health Care Sciences & Services
Saskia von Stillfried, Roman David Buelow, Rainer Roehrig, Peter Boor
Summary: The German COVID-19 Autopsy Registry (DeRegCOVID) serves as a central hub for multicenter autopsy-based studies and provides support for researchers and data analysis. The registry shows that COVID-19 is the underlying cause of death in most autopsy cases, with diffuse alveolar damage and multi-organ failure being the most common immediate causes of death. The registry is of great importance for medical research, policy-making, and public discussion.
LANCET REGIONAL HEALTH-EUROPE
(2022)
Correction
Clinical Neurology
Nelson Ferreira, Mette Richner, Amelia van der Laan, Ida Bergholdt Jul Christiansen, Christian B. Vaegter, Jens R. Nyengaard, Glenda M. Halliday, Joachim Weis, Benoit I. Giasson, Ian R. Mackenzie, Poul H. Jensen, Asad Jan
BRAIN COMMUNICATIONS
(2022)
Article
Critical Care Medicine
Saskia von Stillfried, Roman David Buelow, Rainer Roehrig, Patrick Meybohm, Peter Boor
Summary: This study analyzed data from the German COVID-19 autopsy registry and found that bleeding events were more frequent in ECMO cases, with a higher proportion of intracranial bleeding. The study suggests the potential value of autopsies and a joint interdisciplinary multicenter approach in addressing fatal complications in COVID-19.