Review
Biochemistry & Molecular Biology
Peter G. E. Kennedy, Woro George, Xiaoli Yu
Summary: The etiology of multiple sclerosis (MS) remains unclear. There is controversy regarding whether neural cell apoptosis is the key event initiating and driving the pathological cascade, and the role of inflammation-independent and cell autonomous neuronal processes in axonal damage needs further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Lara-Jasmin Schroeder, Felix Mulenge, Andreas Pavlou, Thomas Skripuletz, Martin Stangel, Viktoria Gudi, Ulrich Kalinke
Summary: In this study, the researchers investigated the transcriptomic signatures of astrocytes during demyelination and remyelination in the cuprizone mouse model. They found that reactive astrocytes showed an inflammatory response during demyelination, while during remyelination, there was a shift towards tissue remodeling and regeneration. These findings highlight the dynamic nature of astrocyte functions during neurodegeneration and regeneration.
Article
Clinical Neurology
Axel Petzold, Sharon Y. L. Chua, Anthony P. Khawaja, Pearse A. Keane, Peng T. Khaw, Charles Reisman, Baljean Dhillon, Nicholas G. Strouthidis, Paul J. Foster, Praveen J. Patel
Summary: The study tested the feasibility of using retinal optical coherence tomography (OCT) measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. The results showed that the inter-eye difference of inner retinal OCT data has potential diagnostic value for multiple sclerosis. The discriminatory power of diagnosing multiple sclerosis using these measures was higher compared to other methods and may be considered as supportive measurements for diagnostic criteria.
Article
Cell Biology
Beatrice Vignoli, Marco Canossa
Summary: This study assessed the contribution of BDNF to synaptic strengthening by deleting TrkB in cortical astrocytes. The results showed that TrkB signaling in astrocytes is not essential for transducing BDNF activity for synaptic potentiation.
Article
Chemistry, Medicinal
Pawel Grieb, Maciej Swiatkiewicz, Agnieszka Kaminska, Anselm Junemann, Robert Rejdak, Konrad Rejdak
Summary: In remitting-relapsing multiple sclerosis, autoreactive immune cells drive relapses while oligodendroglial cells repair myelin during remissions. Disease-modifying therapies can inhibit myelin damage or promote repair, but currently approved therapies are highly toxic. Enhancing myelin repair is a significant unmet medical need for MS patients.
Review
Clinical Neurology
Hans Lassmann
Summary: Neuropathology plays a crucial role in understanding multiple sclerosis (MS) and other inflammatory demyelinating diseases, helping differentiate different diseases, understanding disease progression and damage mechanisms, and providing important guidance for disease treatment and clinical trials.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Ermelinda De Meo, Loredana Storelli, Lucia Moiola, Angelo Ghezzi, Pierangelo Veggiotti, Massimo Filippi, Maria A. Rocca
Summary: In pediatric multiple sclerosis patients, the thalamus undergoes various pathological changes including focal lesions, microstructural damage, and atrophy. Utilizing multiparametric magnetic resonance imaging allows for the detection of these changes in relation to the distance from the thalamus to the CSF and white matter.
Article
Biochemistry & Molecular Biology
Jacopo Angelini, Davide Marangon, Stefano Raffaele, Davide Lecca, Maria P. Abbracchio
Summary: The study identified a significant increase of GPR17-expressing cells in multiple sclerosis (MS) patients, mainly accumulating in the normal appearing white matter (NAWM) with moderate inflammation. Additionally, two distinct subpopulations of GPR17-expressing oligodendroglial cells were found in the white matter of healthy controls and MS patients, characterized by different morphologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Martina Kunkl, Carola Amormino, Valentina Tedeschi, Maria Teresa Fiorillo, Loretta Tuosto
Summary: This review summarizes the changes and behavior of astrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis, as well as the contribution of pathogenic T cell subsets and CD8(+) T cells to astrocytic modifications and pathological outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Heinig Leo, Markus Kipp
Summary: Remyelination therapies are crucial in the treatment of multiple sclerosis, and the cuprizone model is a widely used model to study the effectiveness of new compounds. This review article summarizes recent findings using this model and discusses the potential of identified compounds in promoting remyelination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Seyedmousa Motavallihaghi, Mojgan Ghaemipanaeian, Sara Soleimani Asl, Faeze Foroughi-Parvar, Amir Hossein Maghsood
Summary: This study aimed to investigate the effect of Toxoplasma gondii infection on a multiple sclerosis (MS) mouse model. The results showed that chronic toxoplasmosis could inhibit the development of MS, reduce clinical symptoms, and decrease the levels of inflammatory cells and cytokines. These findings suggest that chronic toxoplasmosis may have therapeutic potential for MS.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Feng-Yi Yang, Li-Hsin Huang, Meng-Ting Wu, Zih-Yun Pan
Summary: This study explored the effects of low-intensity pulsed ultrasound (LIPUS) on remyelination and resident cells in a demyelination model. The results showed that LIPUS can significantly increase myelin basic protein (MBP) expression, inhibit glial cell activation, enhance mature oligodendrocyte density, and promote brain-derived neurotrophic factor (BDNF) expression at the lesion site. In addition, LIPUS treatment resulted in the presence of a heterogeneous population of microglia with various morphologies in the demyelination lesion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Merel Rijnsburger, Niek Djuric, Inge A. Mulder, Helga E. de Vries
Summary: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, with significant impact on patients and their proxies. Obesity is associated with an increased risk of developing MS. Adipokines play a crucial role in MS pathology and may have therapeutic potential in targeting neuroinflammation and neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Clinical Neurology
Xue Zhang, Fang Chen, Mingyue Sun, Nan Wu, Bin Liu, Xiangming Yi, Ruli Ge, Xueli Fan
Summary: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that causes disability in young adults. The damage to myelin, oligodendrocytes, and axons is the characteristic feature of MS. Microglia play important roles in CNS surveillance, neurogenesis, synaptic refinement, and myelin pruning, but their continuous activation can contribute to neurodegeneration.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Mohammad Bakhtiari, Nazem Ghasemi, Hossein Salehi, Noushin Amirpour, Mohammad Kazemi, Mohammad Mardani
Summary: The study demonstrates that the combination of Edaravone with hADSCs effectively reduces demyelination and increases oligodendrogenesis in the multiple sclerosis models.
Article
Endocrinology & Metabolism
Roberto Oleari, Valentina Andre, Antonella Lettieri, Sophia Tahir, Lise Roth, Alyssa Paganoni, Ivano Eberini, Chiara Parravicini, Valeria Scagliotti, Ludovica Cotellessa, Francesco Bedogni, Lisa Benedetta De Martini, Maria Vittoria Corridori, Simona Gulli, Hellmut G. Augustin, Carles Gaston-Massuet, Khalid Hussain, Anna Cariboni
Summary: In this study, researchers aimed to assess the role of mutated Semaphorin 3G (SEMA3G) in causing a syndromic form of HH characterized by intellectual disability and facial dysmorphic features. Through homozygosity mapping and exome sequencing, a novel variant in the SEMA3G gene was identified. Using mouse models, in silico homology modelling, and in vitro cell culture assays, it was found that SEMA3G regulates the migration of GnRH neurons and mutations in SEMA3G affect receptor selectivity which may contribute to HH-related defects.
NEUROENDOCRINOLOGY
(2021)
Article
Clinical Neurology
Cathleen Hagemann, Giulia E. Tyzack, Doaa M. Taha, Helen Devine, Linda Greensmith, Jia Newcombe, Rickie Patani, Andrea Serio, Raphaelle Luisier
Summary: Machine learning techniques were used to analyze high-content microscopy data of motor neurons from ALS post-mortem tissue sections, identifying distinct MN subpopulations in mutant transgenic mice and establishing scoring metrics to rank cells and tissue samples for disease probability and severity. This approach validated that morphological descriptors can effectively discriminate ALS from control tissue at the single cell level, potentially transforming our understanding of ALS and neurodegeneration.
Article
Medicine, Research & Experimental
Linda Scaramuzza, Giuseppina De Rocco, Genni Desiato, Clementina Cobolli Gigli, Martina Chiacchiaretta, Filippo Mirabella, Davide Pozzi, Marco De Simone, Paola Conforti, Massimiliano Pagani, Fabio Benfenati, Fabrizia Cesca, Francesco Bedogni, Nicoletta Landsberger
Summary: MECP2 mutations cause Rett syndrome, affecting females and altering early brain development. Increasing neuronal activity may delay specific RTT phenotypes.
EMBO MOLECULAR MEDICINE
(2021)
Review
Neurosciences
Carole Escartin, Elena Galea, Andras Lakatos, James P. O'Callaghan, Gabor C. Petzold, Alberto Serrano-Pozo, Christian Steinhauser, Andrea Volterra, Giorgio Carmignoto, Amit Agarwal, Nicola J. Allen, Alfonso Araque, Luis Barbeito, Ari Barzilai, Dwight E. Bergles, Gilles Bonvento, Arthur M. Butt, Wei-Ting Chen, Martine Cohen-Salmon, Colm Cunningham, Benjamin Deneen, Bart De Strooper, Blanca Diaz-Castro, Cinthia Farina, Marc Freeman, Vittorio Gallo, James E. Goldman, Steven A. Goldman, Magdalena Gotz, Antonia Gutierrez, Philip G. Haydon, Dieter H. Heiland, Elly M. Hol, Matthew G. Holt, Masamitsu Iino, Ksenia V. Kastanenka, Helmut Kettenmann, Baljit S. Khakh, Schuichi Koizumi, C. Justin Lee, Shane A. Liddelow, Brian A. MacVicar, Pierre Magistretti, Albee Messing, Anusha Mishra, Anna V. Molofsky, Keith K. Murai, Christopher M. Norris, Seiji Okada, Stephane H. R. Oliet, Joao F. Oliveira, Aude Panatier, Vladimir Parpura, Marcela Pekna, Milos Pekny, Luc Pellerin, Gertrudis Perea, Beatriz G. Perez-Nievas, Frank W. Pfrieger, Kira E. Poskanzer, Francisco J. Quintana, Richard M. Ransohoff, Miriam Riquelme-Perez, Stefanie Robel, Christine R. Rose, Jeffrey D. Rothstein, Nathalie Rouach, David H. Rowitch, Alexey Semyanov, Swetlana Sirko, Harald Sontheimer, Raymond A. Swanson, Javier Vitorica, Ina-Beate Wanner, Levi B. Wood, Jiaqian Wu, Binhai Zheng, Eduardo R. Zimmer, Robert Zorec, Michael V. Sofroniew, Alexei Verkhratsky
Summary: The article highlights the challenges and uncertainties surrounding reactive astrocytes, advocating for comprehensive research that includes assessment of multiple molecular and functional parameters, preferably in vivo, along with multivariate statistics and determination of impact on pathological hallmarks in relevant models.
NATURE NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Emanuela Colombo, Cinthia Farina
Summary: Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that binds to specific G protein-coupled receptors expressed in various organs. Targeting S1P receptors with modulators has shown potential in treating neurological, autoimmune, and inflammatory disorders. These modulators induce lymphopenia and may have immunological effects beyond lymphocyte trafficking inhibition. They can also cross the blood-brain barrier and target CNS resident cells expressing S1P receptors. Understanding the role of S1P signaling in neuroimmunology has important implications for therapeutic approaches in other disease areas.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Anna-Leigh Brown, Oscar G. Wilkins, Matthew J. Keuss, Sarah E. Hill, Matteo Zanovello, Weaverly Colleen Lee, Alexander Bampton, Flora C. Y. Lee, Laura Masino, Yue A. Qi, Sam Bryce-Smith, Ariana Gatt, Martina Hallegger, Delphine Fagegaltier, Hemali Phatnani, Jia Newcombe, Emil K. Gustavsson, Sahba Seddighi, Joel F. Reyes, Steven L. Coon, Daniel Ramos, Giampietro Schiavo, Elizabeth M. C. Fisher, Towfique Raj, Maria Secrier, Tammaryn Lashley, Jernej Ule, Emanuele Buratti, Jack Humphrey, Michael E. Ward, Pietro Fratta
Summary: Risk variants in the synaptic gene UNC13A are associated with increased risk of ALS and FTD. These variants lead to the inclusion of a cryptic exon in UNC13A when TDP-43 is depleted, resulting in the loss of UNC13A protein. Two common UNC13A polymorphisms strongly associated with ALS and FTD risk overlap with TDP-43 binding sites.
Article
Medicine, Research & Experimental
Cristina Rivellini, Emanuela Porrello, Giorgia Dina, Simona Mrakic-Sposta, Alessandra Vezzoli, Marco Bacigaluppi, Giorgia Serena Gullotta, Linda Chaabane, Letizia Leocani, Silvia Marenna, Emanuela Colombo, Cinthia Farina, Jia Newcombe, Klaus-Armin Nave, Ruggero Pardi, Angelo Quattrini, Stefano C. Previtali
Summary: Oligodendrocytes are the primary target of demyelinating disorders. Lack of CSN5 (JAB1) expression leads to cellular senescence, chronic inflammation, and oxidative stress, resulting in CNS demyelination, neuroinflammation, and neurodegeneration.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Cell Biology
Francesca Grassivaro, Gianvito Martino, Cinthia Farina
Summary: Microglia, the tissue resident macrophages of the brain, play a key role in central nervous system development and homeostasis. While specific markers have been identified for their investigation, recent studies have shown that their phenotype is constantly shaped by the microenvironment, leading to unexpected phenotypic convergence between microglia and peripheral macrophages at certain developmental stages and under pathological conditions. This novel information sheds new light on the therapeutic potential for neuroinflammatory and neurodegenerative diseases.
NEURAL REGENERATION RESEARCH
(2021)