Article
Clinical Neurology
Sara Salvany, Anna Casanovas, Lidia Piedrafita, Silvia Gras, Jordi Caldero, Josep E. Esquerda
Summary: Early misfolded superoxide dismutase 1 (mfSOD1) accumulation, motor neuron (MN) degeneration, and microgliosis are hallmark pathological features in SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice. Different MN subtypes exhibit varying vulnerabilities, leading to the coexistence of degenerating and surviving MNs during disease progression. The most severe phenotype is observed in fast-twitch subtype MNs, which display high levels of mfSOD1 and extensive vacuolar degeneration. Vacuoles, originating from mitochondria, contain mfSOD1 along with nonmitochondrial proteins. The fusion of ER-derived vesicles enriched with mfSOD1 and outer mitochondrial membranes is believed to be the main mechanism for vacuole formation. Vacuolar degeneration occurs transiently in the presymptomatic stages of ALS, and vacuolated MNs also express the effector protein pMLKL, suggesting a mechanism involving extracellular vesicles in neuroinflammation and disease spreading. Additionally, the expression of mfSOD1 and local neuroinflammation demonstrate bidirectional communication, as manipulation of microglial response affects MN phenotypes. Detailed understanding of these processes prior to the end stages of the disease is essential for identifying novel therapeutic targets.
Article
Neurosciences
Elena Obrador, Rosario Salvador, Patricia Marchio, Rafael Lopez-Blanch, Ali Jihad-Jebbar, Pilar Rivera, Soraya L. Valles, Salvador Banacloche, Javier Alcacer, Nuria Colomer, Javier A. Coronado, Sandra Alandes, Eraci Drehmer, Maria Benlloch, Jose M. Estrela
Summary: Research showed that the combination of nicotinamide riboside and pterostilbene significantly improved neuronal activity and coordination in ALS patients and transgenic mice. These molecules not only prolonged survival in mice but also reduced inflammation associated with ALS progression.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Edoardo Nicolo Aiello, Debora Pain, Alice Radici, Kalliopi Marinou Aktipi, Riccardo Sideri, Ildebrando Appollonio, Gabriele Mora
Summary: This study found cognitive deficits in ALS patients, with classical and predominant-upper motor neuron phenotypes performing the worst. Poorer functional scores correlated with poorer cognitive scores. These findings are important for understanding the cognitive impact of ALS.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Sara Hernandez, Sara Salvany, Anna Casanovas, Lidia Piedrafita, M. Clara Soto-Bernardini, Olga Tarabal, Alba Blasco, Silvia Gras, Alao Gatius, Markus H. Schwab, Jordi Caldero, Josep E. Esquerda
Summary: This article investigates the therapeutic impact of neuregulin-1 (NRG1) on amyotrophic lateral sclerosis (ALS). Using a transgenic mouse model, the study finds that enhanced NRG1 signaling does not significantly improve the pathological features of SOD1-induced disease, but instead accelerates disease onset and worsens motor phenotype.
Review
Cell Biology
Ting-Jung Lin, Guang-Chao Cheng, Luo-Yun Wu, Wei-Yu Lai, Thai-Yen Ling, Yung-Che Kuo, Yen-Hua Huang
Summary: Cellular therapy has shown potential as a treatment for ALS, but its safety and efficacy are still a topic of debate. This review summarizes the current progress and discusses the pros and cons of different types of cell therapy, with a focus on mesenchymal stem cells in ALS.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Clinical Neurology
B. A. Ashford, D. Boche, J. Cooper-Knock, P. R. Heath, J. E. Simpson, J. R. Highley
Summary: Microglia play a crucial role in Motor Neuron Disease (MND), influencing both inflammatory progression and potential protection against the disease. Further research is needed to fully understand the role of microglia in MND, particularly in human studies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Tereza Filipi, Zuzana Matusova, Pavel Abaffy, Ondrej Vanatko, Jana Tureckova, Sarka Benesova, Monika Kubiskova, Denisa Kirdajova, Jakub Zahumensky, Lukas Valihrach, Miroslava Anderova
Summary: This study comprehensively investigates the disease-related activity of glia in the cortex of SOD1(G93A) mice using single-cell RNA sequencing and immunohistochemistry techniques. The results show minimal changes in glia throughout disease progression and regardless of sex. However, there were subtle disease-related transcriptional alterations in microglia and oligodendrocytes at the end-stage, supported by immunohistochemistry. Therefore, it is recommended to use a different model for future studies of the cortical ALS pathology.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Nicol Birsa, Agnieszka M. Ule, Maria Giovanna Garone, Brian Tsang, Francesca Mattedi, P. Andrew Chong, Jack Humphrey, Seth Jarvis, Melis Pisiren, Oscar G. Wilkins, Micheal L. Nosella, Anny Devoy, Cristian Bodo, Rafaela Fernandez de la Fuente, Elizabeth M. C. Fisher, Alessandro Rosa, Gabriella Viero, Julie D. Forman-Kay, Giampietro Schiavo, Pietro Fratta
Summary: Mutations in FUS lead to its mislocalization in the cytoplasm, affecting the sequestration and repression of translation of another RBP, FMRP, in motor neurons associated with ALS.
Article
Biochemistry & Molecular Biology
Cecilia Simonini, Elisabetta Zucchi, Roberta Bedin, Ilaria Martinelli, Giulia Gianferrari, Nicola Fini, Gianni Soraru, Rocco Liguori, Veria Vacchiano, Jessica Mandrioli
Summary: The study found that CSF pNfH is significantly higher in classic and UMNp-ALS patients, and can differentiate them from UMN diseases with a better prognosis such as PLS and hSP. CSF pNfH independently predicted survival in UMN patients and classic/bulbar ALS, while in UMNp-ALS patients, the progression rate and presence of multifocal fasciculations were independent prognostic factors.
Article
Clinical Neurology
Edoardo Nicolo Aiello, Antonella Esposito, Ilaria Giannone, Lorenzo Diana, Susan Woolley, Jennifer Murphy, Georgia Christodoulou, Lucio Tremolizzo, Nadia Bolognini, Ildebrando Appollonio
Summary: The study aimed to standardize the ALS-CBS (TM)-PhV for the Italian population, a telephone-based screening for frontotemporal dysfunction in MND patients. Results showed that the screening test was statistically reliable for assessing frontotemporal disorders and could improve tele-healthcare for MND patients, with epidemiological applications and effective assessments in decentralized clinical trials.
NEUROLOGICAL SCIENCES
(2022)
Article
Cell Biology
Veronica Granatiero, Nicole M. Sayles, Angela M. Savino, Csaba Konrad, Michael G. Kharas, Hibiki Kawamata, Giovanni Manfredi
Summary: ALS is a complex disease involving motor neuron degeneration, with emerging evidence suggesting the importance of astrocytes and the MTOR pathway in disease pathogenesis. Modulation of the astrocytic IGF1R-MTOR pathway may present a potential therapeutic strategy for SOD1 ALS and other neurological disorders.
Article
Clinical Neurology
Kathrin Muller, Ki-Wook Oh, Angelica Nordin, Sudhan Panthi, Seung Hyun Kim, Frida Nordin, Axel Freischmidt, Albert C. Ludolph, Chang Seok Ki, Karin Forsberg, Jochen Weishaupt, Young-Eun Kim, Peter Munch Andersen
Summary: De novo mutations in SOD1 have been identified as a cause of sporadic ALS, potentially impacting both isolated cases and smaller familial groups. While the exact origin of these mutations remains uncertain, the findings suggest the importance of genetic counseling and screening for all ALS patients to potentially benefit from personalized therapy.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Neurosciences
Lauren F. Borkowski, Amy N. Keilholz, Catherine L. Smith, Kaylie A. Canda, Nicole L. Nichols
Summary: This study utilized a CTB-SAP rodent model to investigate the effects of motor neuron death on the output of surviving phrenic motor neurons, revealing different outcomes at different time points. Factors contributing to enhancing or constraining phrenic long-term facilitation were explored.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Sunny Kumar, Daniel Phaneuf, Pierre Cordeau, Hejer Boutej, Jasna Kriz, Jean-Pierre Julien
Summary: The study revealed that inducing autophagy reduces TDP-43 pathology and improves translational defects in ALS/FTD mouse models. Oral administration of IMS-088 can restore translational defects associated with TDP-43 proteinopathy and enhance the synthesis of neurofilament proteins.
MOLECULAR NEURODEGENERATION
(2021)
Article
Clinical Neurology
Adriaan D. de Jongh, Nathalie Braun, Markus Weber, Michael A. van Es, Pegah Masrori, Jan H. Veldink, Philip van Damme, Leonard H. van den Berg, Ruben P. A. van Eijk
Summary: This study aimed to characterize disease progression in amyotrophic lateral sclerosis (ALS) according to the Gold Coast criteria (GCC). The results showed that the GCC broadened the definition of ALS, allowing more patients to participate in trials, while minimally impacting population heterogeneity. However, there were variations in survival time and progression rates between different diagnostic categories, suggesting that selecting specific categories for trials may not result in a more homogeneous study population.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Neurosciences
Li-Pao Fang, Qing Liu, Erika Meyer, Anna Welle, Wenhui Huang, Anja Scheller, Frank Kirchhoff, Xianshu Bai
Summary: Oligodendrocyte precursor cells (OPCs) are uniformly distributed in the mammalian brain, but their function varies depending on their origin, location, receptor/channel expression, and age. A subset of OPCs lacking Olig2 was identified in various brain regions, most commonly in the juvenile brain and rarely in the adult brain. These cells do not proliferate and have a less complex morphology compared to OPCs that express Olig2. They prefer to remain in a precursor stage and do not differentiate into highly branched oligodendrocytes. Changes in the brain activity can stimulate the transition of OPCs with Olig2 expression to OPCs without Olig2.
Article
Clinical Neurology
Anna Lena Fisse, Jeremias Motte, Thomas Grueter, Felix Kohle, Cornelius Kronlage, Jan-Hendrik Stahl, Natalie Winter, Tabea Seeliger, Stefan Gingele, Frauke Stascheit, Benjamin Hotter, Juliane Klehmet, Karsten Kummer, Elena K. Enax-Krumova, Dietrich Sturm, Thomas Skripuletz, Jens Schmidt, Min-Suk Yoon, Kalliopi Pitarokoili, Helmar C. Lehmann, Alexander Grimm
Summary: This study investigates the current care of patients with immune-mediated polyneuropathies in specialized centers in Germany and provides important epidemiological insights. The findings suggest that the development of specific treatment and follow-up recommendations is necessary to ensure a uniform standard of patient care.
Article
Neurosciences
Marianne Lizeth Martinez-Mendoza, Cynthia Alejandra Rodriguez-Arzate, Gabriela B. Gomez-Gonzalez, Frank Kirchhoff, Ataulfo Martinez-Torres
Summary: We identified a novel group of cells in the dorsal section of the aqueduct of Sylvius, called dorsal aqueduct niche or DAN, which express glial/stem cell markers and have the potential to generate new cells. These cells resemble tanycytes of the third ventricle and may act as a niche for glial cell generation in the adult mouse brain.
NEUROSCIENCE RESEARCH
(2023)
Review
Clinical Neurology
Emeline Buttigieg, Anja Scheller, Bilal El Waly, Frank Kirchhoff, Franck Debarbieux
Summary: Multiple sclerosis (MS) is a neurodegenerative disease characterized by myelin loss, axonopathy, and inflammation in the central nervous system. Animal models have been developed to study the pathomechanisms of MS and recent advances in imaging techniques have allowed for in vivo analysis. This review provides an overview of current MS animal models and emphasizes the importance of multimodal approaches to improve our understanding of the disease and reduce animal usage.
Article
Neurosciences
Lisa A. Hassel, Franziska Froeb, Melanie Kuespert, Simone Hillgaertner, Philipp Arnold, Wenhui Huang, Frank Kirchhoff, Michael Wegner
Summary: The transcription factor Sox9 plays an important role in neuroepithelial precursors, conferring them with glial competence in the central nervous system. It is crucial for astroglial and oligodendroglial specification. Sox9 is expressed in oligodendrocyte progenitor cells (OPCs) during development, but is turned off in differentiating oligodendrocytes and adult OPCs. By studying mouse models, it has been found that Sox9 enhances oligodendrogenesis during development, but its expression in adult OPCs leads to their conversion into myelinating oligodendrocytes. This suggests that increased levels of Sox9 in adult OPCs may enhance their remyelination capacity, which is important in demyelinating diseases like Multiple Sclerosis.
Correction
Clinical Neurology
V Bril, A. Druzdz, J. Grosskreutz
Article
Cell Biology
Evangelia Xingi, Paraskevi N. Koutsoudaki, Irini Thanou, Minh-Son Phan, Maria Margariti, Anja Scheller, Jean-Yves Tinevez, Frank Kirchhoff, Dimitra Thomaidou
Summary: The Neurovascular Unit (NVU) consists of multiple types of cells and is important for the functioning of the central nervous system (CNS). Neuroinflammation, often seen in neurodegenerative diseases, affects the activity of microglia and astrocytes. This study used imaging techniques to observe the changes in morphology and interactions between the cells and blood vessels in a mouse model of neuroinflammation. The results showed that activated astrocytes lose their normal connection with blood vessels, possibly contributing to a loss of blood-brain barrier integrity, while microglial cells become more physically connected to the blood vessels. These changes persist for several days after neuroinflammation induction.
Article
Clinical Neurology
Christopher Nelke, Christina B. Schroeter, Lukas Theissen, Corinna Preusse, Marc Pawlitzki, Saskia Raeuber, Vera Dobelmann, Derya Cengiz, Felix Kleefeld, Andreas Roos, Benedikt Schoser, Anna Brunn, Eva Neuen-Jacob, Jana Zschuentzsch, Sven G. Meuth, Werner Stenzel, Tobias Ruck
Summary: Inclusion body myositis (IBM) is characterized by the prominent senescence of tissue-resident fibro-adipogenic progenitors (FAPs), which may drive the disease progression of IBM. This study also demonstrates alterations in the phenotypical landscape of muscle-resident cells and skeletal muscle cell dysfunction in IBM. The findings suggest that targeting FAP senescence and maintaining muscle cell health may provide potential therapeutic strategies for IBM.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Hannah Wilcke, Stefanie Glaubitz, Fabian Kueck, Christoph Anten, David Liebetanz, Jens Schmidt, Jana Zschuentzsch
Summary: This study analyzed a clinical record database of MG patients and found that high body mass index and high disease severity were significantly associated with decreased disease-specific quality of life. In addition, female MG patients had significantly poorer quality of life compared to male patients, and women were more impaired in their daily activities compared to men.
Article
Biochemistry & Molecular Biology
Luisa Werner, Michael Gliem, Nicole Rychlik, Goran Pavic, Laura Reiche, Frank Kirchhoff, Markley Silva Oliveira Junior, Joel Gruchot, Sven G. Meuth, Patrick Kuery, Peter Goettle
Summary: Stroke leads to persistent disability due to insufficient treatment strategies. After injury, oligodendroglial precursor cells (OPCs) compensate for myelin loss and prevent axonal loss, but the process is inefficient. Phenotypic screening identified substances that promote myelin repair. The adult organotypic coronal slice culture (OCSC) system provides a resource-efficient model to study repair after stroke.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Genetics & Heredity
Alessandra Ferlini, Edith Sky Gross, Nicolas Garnier
Summary: The era of genomics medicine has brought numerous benefits to rare diseases. Major breakthroughs have been made in disease gene discovery, bioinformatics innovation, and the development of patient data registries and omics repositories. Rare diseases have also become the first diseases to benefit from nucleic acid-based therapies.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Clinical Neurology
Vera Bril, Artur Druzdz, Julian Grosskreutz, Ali A. Habib, Renato Mantegazza, Sabrina Sacconi, Kimiaki Utsugisawa, John Vissing, Tuan Vu, Marion Boehnlein, Ali Bozorg, Maryam Gayfieva, Bernhard Greve, Franz Woltering, Henry J. Kaminski
Summary: This study evaluated the safety and efficacy of Rozanolixizumab for generalised myasthenia gravis. The results showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes, and both doses (7 mg/kg and 10 mg/kg) were well tolerated. These findings support the mechanism of action of neonatal Fc receptor inhibition in generalised myasthenia gravis, and Rozanolixizumab represents a potential additional treatment option for patients with this condition.
Article
Clinical Neurology
James F. Howard Jr, Saskia Bresch, Angela Genge, Channa Hewamadduma, John Hinton, Yessar Hussain, Raul Juntas-Morales, Henry J. Kaminski, Angelina Maniaol, Renato Mantegazza, Masayuki Masuda, Kumaraswamy Sivakumar, Marek Smilowski, Kimiaki Utsugisawa, Tuan Vu, Michael Weiss, Malgorzata Zajda, Babak Boroojerdi, Melissa Brock, Guillemette de la Borderie, Petra W. Duda, Romana Lowcock, Mark Vanderkelen, M. Isabel Leite
Summary: This study evaluated the safety, efficacy, and tolerability of Zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis. The results showed that patients receiving Zilucoplan treatment had significant improvements in self-perceived ability, disease activity, and myasthenia gravis score compared to the placebo group, with good safety and tolerability. This study provides a new potential treatment option for patients with AChR-positive generalised myasthenia gravis.
Meeting Abstract
Rheumatology
Stefanie Meyer, Leila Scholle, Sabrina Zechel, Susann Kummer, Lennart Kazmaier, Rosa Goetze, Karsten Kummer, Stephan Zierz, Christine Stadelmann, Stephan Sehmisch, Heiko M. Lorenz, Anna K. Hell, Jana Zschuentzsch, Jens Schmidt
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2023)
Review
Clinical Neurology
Emeline Buttigieg, Anja Scheller, Bilal El Waly, Frank Kirchhoff, Franck Debarbieux
Summary: This review provides an overview of animal models of multiple sclerosis (MS) and emphasizes the importance of current imaging modalities at the microscopic and macroscopic levels. The review highlights the significance of using multimodal approaches to enhance our understanding of the disease and minimize the use of animals.