Article
Clinical Neurology
Jordi Duran, Arnau Hervera, Kia H. Markussen, Olga Varea, Iliana Lopez-Soldado, Ramon C. Sun, Jose Antonio del Rio, Matthew S. Gentry, Joan J. Guinovart
Summary: Recent studies have shown that Lafora bodies are also present in astrocytes, not only in neurons. Blocking glycogen synthesis in astrocytes prevents the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malin(KO) model.
Article
Neurosciences
Olga Varea, Jordi Duran, Monica Aguilera, Neus Prats, Joan J. Guinovart
Summary: Lafora disease (LD) is a fatal adolescence-onset neurodegenerative condition characterized by the accumulation of aberrant glycogen aggregates known as Lafora bodies (LBs). Early suppression of glycogen synthase (MGS) can prevent LB formation and pathological manifestations of LD, but it is unclear whether late suppression of MGS can halt LB accumulation. Further research is needed to understand the potential therapeutic effects of targeting MGS in LD treatment.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Cell Biology
Jordi Duran
Summary: Lafora disease is a rare disorder caused by mutations in the EPM2A or NHLRC1 gene, resulting in the accumulation of poorly branched glycogen known as Lafora bodies in the brain and other tissues. While it was previously believed that these glycogen aggregates only accumulated in neurons, recent research has shown that astrocytes also play a significant role in the pathology of the disease. Understanding the involvement of astrocytes in Lafora disease has important implications for other conditions characterized by abnormal glycogen accumulation in astrocytes, such as Adult Polyglucosan Body disease and Corpora amylacea buildup in aged brains.
Article
Clinical Neurology
Arunan Selvarajah, Carolina Gorodetsky, Paula Marques, Quratulain Zulfiqar Ali, Anne T. Berg, Alfonso Fasano, Danielle M. Andrade
Summary: Limited information is available about Dravet syndrome (DS) in adults compared to the pediatric population. This study aimed to examine gait and motor manifestations in adults with DS. The findings revealed that motor symptoms and gait worsen progressively as patients with DS age.
Article
Neurosciences
Pasquale Pellegrini, Arnau Hervera, Olga Varea, M. Kathryn Brewer, Iliana Lopez-Soldado, Anna Guitart, Monica Aguilera, Neus Prats, Jose Antonio del Rio, Joan J. Guinovart, Jordi Duran
Summary: Lafora disease (LD) is a fatal childhood-onset dementia characterized by the accumulation of glycogen aggregates in various organs, particularly in the brain. The presence of p62, an autophagy adaptor, plays a role in the formation of these aggregates, suggesting a protective mechanism to mitigate the harmful consequences of glycogen accumulation in the brain.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Behavioral Sciences
Kia H. Markussen, Jessica K. A. Macedo, Maria Machio, Alison Dolce, Y. Paul Goldberg, Craig W. Vander Kooi, Matthew S. Gentry
Summary: Lafora disease is a fatal childhood dementia with severe epilepsy caused by recessive mutations in EPM2A or EPM2B genes, characterized by abnormal cytoplasmic carbohydrate aggregates called Lafora bodies. The 6th International Lafora Epilepsy Workshop, held online due to the pandemic, brought together nearly 300 clinicians, scientists, and stakeholders to discuss clinical progress, translational research, and novel discoveries in understanding the mechanisms of LD.
EPILEPSY & BEHAVIOR
(2021)
Article
Biology
Thilo von Klopmann, Saija Ahonen, Irene Espadas-Santiuste, Kaspar Matiasek, Daniel Sanchez-Masian, Stefan Rupp, Helene Vandenberghe, Jeremy Rose, Travis Wang, Peixiang Wang, Berge Arakel Minassian, Clare Rusbridge
Summary: Canine Lafora disease is a rapidly progressing neurodegenerative disease caused by a genetic mutation, affecting various breeds of dogs, and genetic testing is necessary for diagnosis.
Article
Clinical Neurology
Yu Wang, Su-yue Wang, Kai Li, Yu-long Zhu, Kun Xia, Dan-dan Sun, Wen-long Ai, Xiao-ming Fu, Qun-rong Ye, Jun Li, Huai-zhen Chen
Summary: Krabbe disease (KD), a rare autosomal recessive condition, usually occurs in infants and young children but can also manifest in adults. This case report describes an adult-onset KD with progressive myoclonic epilepsy and cortical lesions, caused by a homozygous missense mutation in the GALC gene. Brain MRI revealed cortical ribbon sign. This case expands the clinical phenotypes of adult-onset KD.
FRONTIERS IN NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
M. Kathryn Brewer, Maria Machio-Castello, Rosa Viana, Jeremiah L. Wayne, Andrea Kuchtova, Zoe R. Simmons, Sarah Sternbach, Sheng Li, Maria Adelaida Garcia-Gimeno, Jose M. Serratosa, Pascual Sanz, Craig W. Vander Kooi, Matthew S. Gentry
Summary: Lafora disease is a fatal childhood dementia caused by mutations in EPM2A or EPM2B, characterized by progressive myoclonic epilepsy and rapid neurological decline. A pipeline for characterizing laforin missense mutations reveals distinct functional classes associated with different outcomes, providing genetic information for treating LD patients.
Article
Clinical Neurology
Giuseppe d'Orsi, Andrea Farolfi, Lorenzo Muccioli, Orazio Palumbo, Pietro Palumbo, Sergio Modoni, Vincenzo Allegri, Valentina Garibotto, Maria Teresa Di Claudio, Ester Di Muro, Mario Benvenuto, Francesca Bisulli, Massimo Carella
Summary: The study aims to evaluate the electro-clinical features and laboratory and instrumental correlates of neurodegeneration in order to detect the progression of Lafora disease (LD). The results identify three progressive electro-clinical stages and biomarkers that can help evaluate the efficacy of new disease-modifying treatments.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Priyanka Sinha, Bhupender Verma, Subramaniam Ganesh
Summary: Brain aging is characterized by a decline in cellular homeostatic processes, leading to a decreased ability to respond to physiological stress. The aged brain shows physical changes such as degenerating neurons, proteinaceous plaques and tangles, intracellular deposition of glycogen, and elevated neuroinflammation, which are also seen in neurodegenerative disorders. In this study, the authors demonstrate that the expression level of genes implicated in progressive myoclonus epilepsy (PME) decreases with age, resulting in compromised neuronal response and increased susceptibility to seizures. Furthermore, they show that suppressing neuroinflammation can improve seizure susceptibility in both aged animals and animal models of PME.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Cinzia Costa, Karen L. Oliver, Carmen Calvello, Jillian M. Cameron, Valentina Imperatore, Laura Tonelli, Davide Colavito, Silvana Franceschetti, Laura Canafoglia, Samuel F. Berkovic, Paolo Prontera
Summary: Progressive myoclonus epilepsies (PMEs) are a diverse group of neurodegenerative disorders that typically occur in late childhood. Through genome-wide molecular studies, pathogenic variants in the IRF2BPL gene were identified in patients with PME, suggesting its involvement in the disease. These findings expand the phenotypic spectrum of IRF2BPL-related disorders and highlight the importance of considering this gene in the diagnosis of patients with PME.
Article
Clinical Neurology
Fizza Orooj, Umm-e-Kalsoom, XiaoChu Zhao, Arsalan Ahmad, Imran Nazir Ahmed, Muhammad Faheem, Muhammad Jawad Hassan, Berge A. Minasian
Summary: Lafora body disease is a rare glycogen storage disease characterized by accumulation of deformed glycogen molecules in multiple organs, leading to myoclonic epilepsy and ultimately death within 10 years. This case report from a consanguineous family in Pakistan identified a novel mutation in the EPM2A gene, expanding our understanding of the disorder's etiology and mutation spectrum.
Review
Biochemistry & Molecular Biology
Kia H. Markussen, Manuela Corti, Barry J. Byrne, Craig W. Vander Kooi, Ramon C. Sun, Matthew S. Gentry
Summary: This review discusses the primary role of glycogen in carbohydrate storage and energy metabolism in the liver and muscle, as well as its critical metabolic and non-metabolic roles in the brain. Perturbed glycogen functions are observed in various brain disorders, including neurological glycogen storage diseases. The study of glycogen and its treatment strategies is of great significance for human diseases.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Neurosciences
Sara Bernardi, Federica Gemignani, Maria Marchese
Summary: Progressive myoclonic epilepsies (PMEs) are rare neurodegenerative diseases characterized by myoclonus, seizures, and neurological deterioration. The involvement of the cerebellar cortex and the loss of Purkinje cells (PCs) in PMEs are associated with motor impairments and epilepsy. This review focuses on the role of PCs in epilepsy and particularly highlights their involvement in seizure phenotype in neuronal ceroid lipofuscinosis (NCL).
NEUROBIOLOGY OF DISEASE
(2023)
Article
Gastroenterology & Hepatology
Dan Liu, Jean-Claude Marie, Anne-Laure Pelletier, Zhuoyao Song, Marwa Ben-Khemis, Kaouthar Boudiaf, Coralie Pintard, Thibaut Leger, Samuel Terrier, Guillaume Chevreux, Jamel El-Benna, Pham My-Chan Dang
Summary: CK2 is a major partner of NOXO1 in colon epithelial cells under inflammatory conditions. CK2 limits NOX1 activity by directly binding and phosphorylating NOXO1. Reduced CK2 activity during acute colitis results in excessive ROS production and contributes to the pathogenesis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Physiology
B. Allegrini, S. Jedele, L. David Nguyen, M. Mignotet, R. Rapetti-Mauss, C. Etchebest, O. Fenneteau, A. Loubat, A. Boutet, C. Thomas, J. Durin, A. Petit, C. Badens, L. Garcon, L. Da Costa, H. Guizouarn
Summary: Two new mutations on KCNN4, V222L and H340N, were found to increase the calcium sensitivity of the K+ channel, but did not lead to obvious red blood cell dehydration. This raises questions about the role of KCNN4 gain-of-function mutations in hydration status and viability of red blood cells.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bayot Juliette, Martin Caroline, Chevreux Guillaume, Camadro Jean-Michel, Auchere Francoise
Summary: Candida albicans adapts to host microenvironments by remodeling metabolic pathways and antioxidant defenses in response to changes in carbon sources. Glucose, acetate, and lactate induce unique patterns of response in C. albicans cells. The role of cellular redox status regulation and defenses against oxidative stress, including thiol-and glutathione-dependent response, in the adaptive response of C. albicans to alternative carbon sources should be reconsidered.
BIOCHEMICAL JOURNAL
(2023)
Article
Biochemical Research Methods
Laurent Lignieres, Veronique Legros, Manel Khelil, Nicolas Senecaut, Matthew A. Lauber, Jean-Michel Camadro, Guillaume Chevreux
Summary: In top-down proteomics, intact protein ions are fragmented for MS analysis. This approach has been used to study post-translational modifications and clipped forms of proteins. In this study, a silica-based media with phenyl bonding was used in capillary columns for top-down proteomics, and efficient separations were achieved for diverse proteins.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Hematology
Cedric Vrignaud, Mahmoud Mikdar, Romain Duval, Luc Reininger, Vijaya L. Damaraju, Michael Sawyer, Yves Colin, Caroline Le Van Kim, Jean-Christophe Gelly, Catherine Etchebest, Thierry Peyrard, Slim Azouzi
Summary: This study identified a novel high-prevalence antigen, AUG4, in the Augustine blood group system, which is encoded by the rare SLC29A1 variant allele AUG*04 (c.242A > G, p.Asn81Ser). The study provides insights into the molecular structure and potential pathogenic mechanisms of this antigen.
Article
Biochemical Research Methods
Claire Cargemel, Stephanie Marsin, Magali Noiray, Pierre Legrand, Halil Bounoua, Ines Li De la Sierra-Gallay, Helene Walbott, Sophie Quevillon-Cheruel
Summary: During bacterial genome replication initiation, replicative helicases rely on specialized proteins for their loading onto oriC. DnaC and DnaI were the first loaders to be characterized. However, many bacteria do not have these genes and instead have domesticated phage elements that have replaced the original loader gene dciA. A crystal structure study of the complex from Vibrio cholerae revealed that two VcDciA molecules interact with a dimer of VcDnaB without altering its canonical structure, providing insights into how DciA assists in DnaB loading. Surprisingly, DnaC from Escherichia coli also targets the same module on EcDnaB, suggesting functional interchangeability between VcDciA and EcDnaC despite their lack of structural similarity. This study represents a significant advancement in understanding the mechanism by which phage helicase loaders hijack bacterial replicative helicases during evolution.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Plant Sciences
Elena Kazamia, Jan Mach, Jeffrey B. McQuaid, Xia Gao, Tyler H. Coale, Ronald Malych, Jean-Michel Camadro, Emmanuel Lesuisse, Andrew E. Allen, Chris Bowler, Robert Sutak
Summary: This study investigates the localization and dynamics of iron starvation induced proteins (ISIPs) in the model pennate diatom P. tricornutum. The results show that the localization patterns of ISIPs are dependent on the overall iron status of the cell and the source of iron. The study also identifies the involvement of endocytosis machinery in vesicular trafficking and suggests a direct vesicle traffic connection between the diatom cell membrane and the periplastidial compartment (PPC) for proteins involved in iron assimilation.
Article
Biochemical Research Methods
Laurent Lignieres, Nicolas Senecaut, Tien Dang, Laura Bellutti, Marion Hamon, Samuel Terrier, Veronique Legros, Guillaume Chevreux, Gaelle Lelandais, Rene-Marc Mege, Julien Dumont, Jean-Michel Camadro
Summary: The simple light isotope metabolic-labeling technique utilizes U-[12C]-labeled molecules as the sole carbon source for in vivo biosynthesis of amino acids, resulting in the incorporation of U-[12C]-amino acids into proteins. This technique has advantages for mass-spectrometry-based proteomics analysis, providing more intense monoisotopic ions and a better signal-to-noise ratio. The technique has been successfully applied to eukaryotic microorganisms and human cells, as well as an indirect labeling strategy in a nematode model organism.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Laureen Moreaud, Sebastien Viollet, Agathe Urvoas, Marie Valerio-Lepiniec, Agnes Mesneau, Ines Li de la Sierra-Gallay, Jessalyn Miller, Malika Ouldali, Cecile Marcelot, Stephanie Balor, Vanessa Soldan, Cristelle Meriadec, Franck Artzner, Erik Dujardin, Philippe Minard
Summary: A versatile strategy for creating inducible protein assembly with predefined geometry is demonstrated in this article. The assembly is triggered by a binding protein that staples two identical protein bricks together in a predictable spatial conformation. This work opens up possibilities for designing and fabricating multiscale protein origami with arbitrarily programmed shapes and chemical functions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Sofija Vlasevska, Laura Garcia-Ibanez, Romain Duval, Antony B. Holmes, Rahat Jahan, Bowen Cai, Andrew Kim, Tongwei Mo, Katia Basso, Rajesh K. Soni, Govind Bhagat, Riccardo Dalla-Favera, Laura Pasqualucci
Summary: Heterozygous inactivating mutations of KMT2D and CREBBP are common in B cell lymphoma, and they co-occur in a significant number of follicular lymphoma and EZB/C3 diffuse large B cell lymphoma cases. The combination of haploinsufficiency of Crebbp and Kmt2d promotes the expansion of abnormally polarized germinal centers, which is an early event in lymphoma development. These findings highlight the functional and biochemical interaction between Crebbp and Kmt2d, and its implications for the treatment of lymphomas with enhancer defects induced by their combined loss.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Antoine Gedeon, Nour Ayoub, Sebastien Brule, Bertrand Raynal, Gouzel Karimova, Muriel Gelin, Ariel Mechaly, Ahmed Haouz, Gilles Labesse, Helene Munier-Lehmann
Summary: Inosine 5' -monophosphate dehydrogenase (IMPDH) is an enzyme that oxidizes inosine 5' monophosphate into xanthosine 5'-monophosphate. It consists of a core domain for catalytic reaction and a less-conserved Bateman domain. Two classes of bacterial IMPDHs have been classified based on their oligomeric and kinetic properties, with MgATP acting as an activator for Class I and a modulator of oligomeric state for Class II. Analysis of deleted variants and chimeras revealed the Bateman domain's role in the different properties of the two classes.
Article
Multidisciplinary Sciences
Ignacio Fernandez, Lasse Toftdal Dynesen, Youna Coquin, Riccardo Pederzoli, Delphine Brun, Ahmed Haouz, Antoine Gessain, Felix A. Rey, Florence Buseyne, Marija Backovic
Summary: This paper presents the X-ray structure of the receptor binding domain (RBD) from a simian Foamy virus, providing insights into the viral entry mechanism.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Guillaume Postic, Jean Solarz, Cecile Loubiere, Janany Kandiah, Jaysen Sawmynaden, Frederic Adam, Marie Vilaire, Thibaut Leger, Jean-Michel Camadro, Daniella Balduino Victorino, Marie-Claude Potier, Eric Bun, Gautier Moroy, Alexandre Kauskot, Olivier Christophe, Nathalie Janel
Summary: Down syndrome, the most common chromosomal abnormality in humans, is associated with hematologic disorders, including thrombocytopenia. Our study found that overexpression of Dyrk1A in mice led to a decrease in platelet number by 20% but a reduction in bleeding time by 50%. We propose that Dyrk1A indirectly interacts with fibronectin and fibrinogen, resulting in increased levels of these proteins and decreased bleeding.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Microbiology
Mariano Martinez, Julienne Petit, Alejandro Leyva, Adria Sogues, Daniela Megrian, Azalia Rodriguez, Quentin Gaday, Mathildeb Ben Assaya, Maria Magdalena Portela, Ahmed Haouz, Adrien Ducret, Christophe Grangeasse, Pedro M. Alzari, Rosario Duran, Anne Marie Wehenkel
Summary: This study discovered two members of the division apparatus in Corynebacterium glutamicum, Glp and GlpR, highlighting the crucial communication between the division and elongation machineries that could be targeted for anti-mycobacterial drug development. Furthermore, the study revealed that Corynebacteriales have evolved a protein scaffold to control cell division and morphogenesis.
NATURE MICROBIOLOGY
(2023)