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)
Article
Biochemistry & Molecular Biology
Ines ELBini-Dhouib, Maroua Manai, Nour-Elhouda Neili, Soumaya Marzouki, Ghada Sahraoui, Warda Ben Achour, Sondes Zouaghi, Melika BenAhmed, Raoudha Doghri, Najet Srairi-Abid
Summary: The study found that curcumin has anti-inflammatory and antioxidant effects, which can alleviate the symptoms of multiple sclerosis and promote remyelination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Rhona McGonigal, Clare Campbell, Jennifer A. Barrie, Denggao Yao, Madeleine E. Cunningham, Colin L. Crawford, Simon Rinaldi, Edward G. Rowan, Hugh J. Willison
Summary: In Guillain-Barre syndrome (GBS), both axonal and demyelinating variants can be mediated by complement-fixing anti-GM1 ganglioside autoantibodies that target peripheral nerve axonal and Schwann cell (SC) membranes, respectively. This study investigated the mechanisms underlying direct axonal injury and secondary axonal degeneration following glial injury in GBS using genetically modified mice targeting different neuronal and glial membranes. The findings provide insights into primary and secondary axonal injury and contribute to the understanding of GBS pathogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Clinical Neurology
Raphael Schneider, Jiwon Oh
Summary: Multiple sclerosis is an inflammatory disease of the central nervous system with limited treatment options. New experimental therapy, such as Bruton's Tyrosine Kinase Inhibitors (BTKIs), shows potential in targeting the immunopathology of the central nervous system. There are ongoing clinical trials to evaluate the efficacy and safety of BTKIs in different forms of multiple sclerosis.
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
(2022)
Article
Neurosciences
Navnika Gupta, Afsaneh Shirani, Lakshman Arcot Jayagopal, Ezequiel Piccione, Elizabeth Hartman, Rana Khalil Zabad
Summary: Autoantibodies against nodal and paranodal proteins have been found in central and peripheral nervous system demyelinating disorders. This study retrospectively reviewed the charts of six patients who tested positive for these antibodies and described their clinical presentations and diagnostic findings. The study suggests different features that may help clinicians in checking for these antibodies.
Review
Neurosciences
Ying Gao, Lingxin Kong, Shan Liu, Kangding Liu, Jie Zhu
Summary: This study examined the role of neurofascin in the peripheral nervous system, particularly in chronic inflammatory demyelinating polyneuropathy, and its mechanisms and effects. By dissecting the role of cell adhesion molecules and the structure of the node of Ranvier, a thorough analysis of the pathogenesis of CIDP was conducted.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Clinical Neurology
Jun-ichi Kira
Summary: CIDP is an immune-mediated demyelinating disease of the PNS, with NF155(+) CIDP characterized by demyelinating lesions in both the CNS and PNS, due to the upregulation of Th2 and Th1 cytokines resulting from IgG4 class switching, leading to spinal root inflammation and lack of macrophage infiltration in sural nerves.
FRONTIERS IN NEUROLOGY
(2021)
Review
Chemistry, Multidisciplinary
Yan Wang, David Pleasure, Wenbin Deng, Fuzheng Guo
Summary: PARP1 plays a critical role in DNA repair and gene expression, and its dysregulation is associated with immune activation and disease severity. Studies have shown that PARP1 dysfunction is present in the immune and central nervous system of MS patients and animal models, and its function is complex and context-dependent.
Review
Nutrition & Dietetics
Wei-Sheng Lin, Shan-Ju Lin, Pei-Yin Liao, Divya Suresh, Ting-Rong Hsu, Pei-Yu Wang
Summary: The ketogenic diet shows promise as a safe and potentially effective therapy for multiple sclerosis, but more research is needed to confirm its effects and mechanisms.
ADVANCES IN NUTRITION
(2022)
Article
Neurosciences
Chiara Tremolanti, Chiara Cavallini, Laurence Meyer, Christian Klein, Eleonora Da Pozzo, Barbara Costa, Lorenzo Germelli, Sabrina Taliani, Christine Patte-Mensah, Ayikoe-Guy Mensah-Nyagan
Summary: Research suggests that phenylindoleglyoxylamydes (PIGAs) translocator protein (TSPO) ligands may have therapeutic potential in mice with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) that mimics primary progressive multiple sclerosis (PPMS) in humans. Treatment with PIGA1138 significantly reduced clinical symptoms and improved motor function in MOG-EAE mice, while preserving myelin and axonal integrity. PIGA1138 also inhibited immune cell infiltration, reducing inflammation, and increased anti-inflammatory cytokine levels.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Biology
Ilias Kalafatakis, Maria Savvaki, Theodora Velona, Domna Karagogeos
Summary: This review article focuses on the implication of Contactin-1 and Contactin-2 as well as their interactors in demyelinating pathologies in humans. It discusses the organization and function of myelinated axons in the central and peripheral nervous system, highlighting the role of these molecules in myelination. Studies showing the correlation of the two contactins with demyelinating pathologies are reviewed, emphasizing the importance of these recognition molecules in shaping the function of the nervous system.
Article
Neurosciences
Yu Shao, Chen Chen, Tao Zhu, Zengxian Sun, Shufen Li, Lifen Gong, Xinyan Dong, Weida Shen, Linghui Zeng, Yicheng Xie, Peifang Jiang
Summary: A recent study demonstrates the protective role of TRPM2 gene in progressive multiple sclerosis, showing that it improves disease symptoms by regulating NLRP3 inflammasome activation, which suggests a potential therapeutic target for MS.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Multidisciplinary Sciences
Emanuela Colombo, Daniela Triolo, Claudia Bassani, Francesco Bedogni, Marco Di Dario, Giorgia Dina, Evelien Fredrickx, Isabella Fermo, Vittorio Martinelli, Jia Newcombe, Carla Taveggia, Angelo Quattrini, Giancarlo Comi, Cinthia Farina
Summary: The study revealed that TrkB signaling in astrocytes plays a crucial role in demyelination, fostering oligodendrocyte damage and contributing to chronic demyelination in multiple sclerosis. Additionally, the neurotrophin receptor TrkB was found associated with the expression and release of copper ions during neuroinflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Ilona Klejbor, Derya R. Shimshek, Joanna Klimaszewska-Lata, Maria Velasco-Estevez, Janusz Morys, Bartosz Karaszewski, Andrzej Szutowicz, Aleksandra Rutkowska
Summary: The EBI2 receptor plays a critical role in regulating the immune system and remyelination, rather than demyelination, in multiple sclerosis. Despite similar levels of pro-inflammatory cytokines in wild-type and EBI2 knock-out mice in the cuprizone model, EBI2 knock-out mice showed less efficient myelin recovery post-treatment.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
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
Neurosciences
Haitao Tu, Zhi Wei Zhang, Lifeng Qiu, Yuning Lin, Mei Jiang, Sook-Yoong Chia, Yanfei Wei, Adeline S. L. Ng, Richard Reynolds, Eng-King Tan, Li Zeng
Summary: By systematically studying a series of AD and PD pathogenesis markers, as well as mitochondria, mitophagy, and neuroinflammation-related indicators, researchers have identified a set of signature proteins that can help understand the pathology and etiology of PDD and DLB at the molecular level. These findings provide valuable insights into distinguishing between PDD and DLB based on protein markers.
Article
Clinical Neurology
Benjamin J. Cooze, Matthew Dickerson, Rukshikah Loganathan, Lewis M. Watkins, Ethan Grounds, Ben R. Pearson, Ryan Jack Bevan, B. Paul Morgan, Roberta Magliozzi, Richard Reynolds, James W. Neal, Owain W. Howell
Summary: The extent of grey matter demyelination and neurodegeneration in the progressive multiple sclerosis (PMS) brains is associated with more severe disease. The thalamus in PMS is invariably affected by demyelination and has a higher proportion of active inflammatory lesions compared to forebrain cortical tissue. Thalamic neuronal loss is correlated with white matter pathology in other forebrain areas and disease duration and age of death.
Review
Neurosciences
Anusha Jayaraman, Richard Reynolds
Summary: Necroptosis, a non-apoptotic cell death pathway, plays a significant role in Alzheimer's disease by involving multiple molecular mechanisms that interact and contribute to cellular vulnerability at different disease stages. Targeting these diverse pathways for therapeutic intervention remains a challenge due to their complex synergistic or inhibitory effects on each other.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Clinical Neurology
Roberta Magliozzi, Giulia Fadda, Robert A. Brown, Amit Bar-Or, Owain W. Howell, Simon Hametner, Damiano Marastoni, Alberto Poli, Richard Nicholas, Massimiliano Calabrese, Salvatore Monaco, Richard Reynolds
Summary: Leptomeningeal and perivenular infiltrates play important roles in cortical grey matter damage and disease progression in multiple sclerosis (MS). This study investigated the potential gradient of damage in deep grey matter nuclei and found substantial subependymal-in gradient of neuro-axonal loss and microglia activation in active thalamic lesions of progressive MS cases. The presence of increased leptomeningeal and cerebrospinal fluid (CSF) inflammation was associated with the altered graded pathology and more severe disease progression.
ANNALS OF NEUROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rachael Kee, Michelle Naughton, Gavin McDonnell, Owain W. Howell, Denise C. Fitzgerald
Summary: Multiple sclerosis is a chronic immune-mediated disease characterized by demyelination and breakdown of the blood-brain barrier. In the later stages of the disease, neurological disability accumulates independently of acute episodes of demyelination, accompanied by compartmentalized inflammation. Meningeal tertiary lymphoid structures may serve as markers of disease activity.
Article
Neurosciences
Rhian Evans, Lewis M. M. Watkins, Kristen Hawkins, Gabriella Santiago, Constantinos Demetriou, Michelle Naughton, Marie Dittmer, Mark I. I. Rees, Denise Fitzgerald, B. Paul Morgan, James W. W. Neal, Owain W. W. Howell
Summary: A neuropathological study reveals the presence of complement activation products at the brain surfaces, which are associated with underlying pathology and increased complement receptor-positive microglia/macrophages in expanding cortical grey matter lesions, suggesting a potential target for modifying compartmentalized inflammation and cortical demyelination.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Qing Wang, Jialing Zheng, Sven Pettersson, Richard Reynolds, Eng-King Tan
Summary: The neurovascular unit (NVU) consists of vascular cells, glial cells, and neurons. It plays an important role in maintaining the microenvironment homeostasis and the integrity of the blood-brain barrier. Disruption of the NVU and interactions among its components are involved in the pathophysiology of synucleinopathies, characterized by pathological accumulation of α-synuclein. Neuroinflammation contributes to the pathophysiology of synucleinopathies such as Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. This review summarizes the neuroinflammatory response of glial cells and vascular cells in the NVU, as well as the cross-talk between different cell types within the NVU and the influence of α-synuclein on neuroinflammation and disease progression.
Review
Immunology
Joseph D. Quick, Cristian Silva, Jia Hui Wong, Kah Leong Lim, Richard Reynolds, Anna M. Barron, Jialiu Zeng, Chih Hung Lo
Summary: Microglia are innate immune cells in the brain that play a crucial role in immune responses and defense in the central nervous system. They are responsible for phagocytic and autophagic clearance of waste and toxic proteins, relying on lysosomal acidification. Impaired lysosomal acidification in microglia leads to dysfunction and neurodegeneration, while reacidification can reverse neurodegenerative pathology.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Clinical Neurology
Roberta Magliozzi, Owain W. Howell, Massimiliano Calabrese, Richard Reynolds
Summary: Growing evidence suggests a central role for meningeal inflammation in driving multiple sclerosis (MS) pathology. The subarachnoid space and associated meningeal spaces play important roles in the entry and diffusion of immune cells and molecules into the brain tissue. Chronic meningeal inflammation is associated with a more severe clinical course of MS.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Erik Nutma, Nurun Fancy, Maria Weinert, Stergios Tsartsalis, Manuel C. Marzin, Robert C. J. Muirhead, Irene Falk, Marjolein Breur, Joy de Bruin, David Hollaus, Robin Pieterman, Jasper Anink, David Story, Siddharthan Chandran, Jiabin Tang, Maria C. Trolese, Takashi Saito, Takaomi C. Saido, Katharine H. Wiltshire, Paula Beltran-Lobo, Alexandra Phillips, Jack Antel, Luke Healy, Marie-France Dorion, Dylan A. Galloway, Rochelle Y. Benoit, Quentin Amosse, Kelly Ceyzeriat, Aurelien M. Badina, Enikoe Koevari, Caterina Bendotti, Eleonora Aronica, Carola I. Radulescu, Jia Hui Wong, Anna M. Barron, Amy M. Smith, Samuel J. Barnes, David W. Hampton, Paul van der Valk, Steven Jacobson, Owain W. Howell, David Baker, Markus Kipp, Hannes Kaddatz, Benjamin B. Tournier, Philippe Millet, Paul M. Matthews, Craig S. Moore, Sandra Amor, David R. Owen
Summary: Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. However, the expression of 18 kDa Translocator Protein (TSPO) in activated microglia differs between mice and humans, suggesting different phenomena. TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state, and LCP2 and TFEC are potential markers of microglial activation in humans.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Clinical Neurology
B. Cooze, I. Farkas, Y. Leung, H. Yadanar, K. Gerhards, D. Gveric, R. Nicholas, J. W. Neal, D. R. Owen, R. Reynolds, O. W. Howell
MULTIPLE SCLEROSIS JOURNAL
(2022)
Review
Clinical Neurology
Patrick Vanderdonckt, Francesca Aloisi, Giancarlo Comi, Alexander de Bruyn, Hans-Peter Hartung, Inge Huitinga, Tanja Kuhlmann, Claudia F. Lucchinetti, Imke Metz, Richard Reynolds, Hans Lassmann
Summary: The article discusses the significance of brain tissues in multiple sclerosis research and suggests ways to increase the availability of suitable material. The authors propose methods to increase tissue donation and the creation of a registry for accessible tissues.
BRAIN COMMUNICATIONS
(2022)