Article
Neurosciences
Yuanyuan Wang, Roxanne V. Kyauk, Yun-An A. Shen, Luke Xie, Mike Reichelt, Han Lin, Zhiyu Jiang, Hai Ngu, Kimberle Shen, Jacob J. Greene, Morgan Sheng, Tracy J. Yuen
Summary: Disability in multiple sclerosis (MS) is partially caused by the failure of remyelination and progressive neurodegeneration. The role of microglia, especially triggering receptor expressed on myeloid cells 2 (TREM2), in remyelination is significant. In this study, using a mouse model of focal demyelination, we found that TREM2 knockout mice had persistent demyelination and subsequent neurodegeneration lasting more than 6 weeks. Furthermore, TREM2 knockout microglia showed defects in migration and phagocytosis of myelin debris.
Review
Clinical Neurology
Tyrell J. Simkins, Greg J. Duncan, Dennis Bourdette
Summary: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system, with inflammatory attacks leading to demyelination and axonal damage. Currently, there are no approved therapies that can adequately restore myelin or protect axons from degeneration.
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
(2021)
Article
Neurosciences
E. Dustin, A. R. McQuiston, K. Honke, J. P. Palavicini, X. Han, J. L. Dupree
Summary: The reduction of sulfatide in the normal appearing white matter of Multiple Sclerosis (MS) patients suggests that this depletion may occur early in disease development and drive disease progression. Adult-onset sulfatide depletion has limited effects on myelin structure but results in the loss of axonal integrity and deterioration of domain organization accompanied by axonal degeneration. Furthermore, structurally preserved myelinated axons progressively lose the ability to function as myelinated axons. These findings indicate that sulfatide depletion, occurring in the early stages of MS progression, is sufficient to drive the loss of axonal function independent of demyelination and that axonal pathology may occur earlier than previously recognized.
Review
Cell Biology
Greg J. Duncan, Tyrell J. Simkins, Ben Emery
Summary: Oligodendrocytes play a crucial role in myelinating axons, and disruptions in this relationship can lead to axonal dysfunction and neurodegeneration. Understanding the mechanisms behind demyelination and loss of oligodendrocytes is important in developing potential therapeutic strategies for disorders where oligodendrocyte support of axons is compromised.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(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
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
Clinical Neurology
Simon Licht-Mayer, Graham R. Campbell, Arpan R. Mehta, Katie McGill, Alex Symonds, Sarah Al-Azki, Gareth Pryce, Stephanie Zandee, Chao Zhao, Markus Kipp, Kenneth J. Smith, David Baker, Daniel Altmann, Stephen M. Anderton, Yolanda S. Kap, Jon D. Laman, A. Bert, Moses Rodriguez, Robin J. M. Franklin, Siddharthan Chandran, Hans Lassmann, Bruce D. Trapp, Don J. Mahad
Summary: This study identifies a consistent and robust phenomenon called axonal response of mitochondria to demyelination (ARMD) in experimental demyelination models, which is also observed in multiple sclerosis (MS). The increase in mitochondrial content within demyelinated axons is not always accompanied by a proportionate increase in complex IV activity, particularly in highly inflammatory models. The findings highlight the importance of complex IV activity and pave the way for the development of novel neuroprotective therapies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
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.
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)
Article
Biochemistry & Molecular Biology
Eleonora Giagnorio, Claudia Malacarne, Paola Cavalcante, Letizia Scandiffio, Marco Cattaneo, Viviana Pensato, Cinzia Gellera, Nilo Riva, Angelo Quattrini, Eleonora Dalla Bella, Giuseppe Lauria, Renato Mantegazza, Silvia Bonanno, Stefania Marcuzzo
Summary: Amyotrophic lateral sclerosis (ALS) is characterized by the loss of upper and lower motor neurons (UMNs, LMNs) and miR-146a dysregulation may contribute to the pathogenesis of ALS. In this study, miR-146a levels were increased in ALS peripheral nerves and decreased in the serum of ALS patients, suggesting its potential as a diagnostic and prognostic biomarker for the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Neurosciences
Stephen D. Ginsberg, Michael H. Malek-Ahmadi, Melissa J. Alldred, Shaoli Che, Irina Elarova, Yinghua Chen, Freddy Jeanneteau, Thorsten M. Kranz, Moses Chao, Scott E. Counts, Elliott J. Mufson
Article
Biochemistry & Molecular Biology
Juan C. Arevalo, Enrique Hernandez-Jimenez, Ada Jimenez-Gonzalez, Maria Torres-Valle, Roman S. Iwasaki, Roger Lopez-Bellido, Cristina Vicente-Garcia, Raquel E. Rodriguez
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2018)
Article
Neurosciences
Nuria Suelves, Andres Miguez, Saray Lopez-Benito, Gerardo Garcia-Diaz Barriga, Albert Giralt, Elena Alvarez-Periel, Juan Carlos Arevalo, Jordi Alberch, Silvia Gines, Veronica Brito
MOLECULAR NEUROBIOLOGY
(2019)
Article
Endocrinology & Metabolism
Freddy Jeanneteau, Amelie Borie, Moses V. Chao, Michael J. Garabedian
NEUROENDOCRINOLOGY
(2019)
Article
Psychiatry
Andre B. Veras, Moses V. Chao, Mara Getz, Raymond Goetz, Elie Cheniaux, Fabiana L. Lopes, Antonio E. Nardi, Julie Walsh-Messinger, Dolores Malaspin, Thorsten M. Kranz
PSYCHIATRY RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Hui-Lan Hu, Lora A. Shiflett, Mariko Kobayashi, Moses V. Chao, Angus C. Wilson, Ian Mohr, Tony T. Huang
Article
Neurosciences
Stephen D. Ginsberg, Michael H. Malek-Ahmadi, Melissa J. Alldred, Yinghua Chen, Kewei Chen, Moses V. Chao, Scott E. Counts, Elliott J. Mufson
NEUROBIOLOGY OF DISEASE
(2019)
Article
Developmental Biology
Thorsten M. Kranz, Karin L. Lent, Kimberly E. Miller, Moses Chao, Eliot A. Brenowitz
DEVELOPMENTAL NEUROBIOLOGY
(2019)
Article
Neurosciences
Khalil Saadipour, Alexia Tiberi, Sylvia Lomardo, Elena Grajales, Laura Montroull, Noralyn B. Manucat-Tan, John LaFrancois, Michael Cammer, Paul M. Mathews, Helen E. Scharfman, Francesca-Fang Liao, Wilma J. Friedman, Xin-Fu Zhou, Giueseppina Tesco, Moses Chao
MOLECULAR AND CELLULAR NEUROSCIENCE
(2019)
Editorial Material
Multidisciplinary Sciences
Moses V. Chao
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Cell Biology
Carlos Martin-Rodriguez, Minseok Song, Begona Anta, Francisco J. Gonzalez-Calvo, Ruben Deogracias, Deqiang Jing, Francis S. Lee, Juan Carlos Arevalo
JOURNAL OF CELL SCIENCE
(2020)
Article
Anesthesiology
Julia Sanchez-Sanchez, Cristina Vicente-Garcia, Daniel Canada-Garcia, Dionisio Martin-Zanca, Juan C. Arevalo
Summary: Pain serves as a protective mechanism against harmful stimuli, and the NGF/TrkA axis plays a crucial role as a pain mediator. However, the clinical approval of NGF antibodies is hindered due to side effects. This study reveals that ARMS/Kidins220, a scaffold protein for Trk receptors, modulates nociception. Reduction of ARMS/Kidins220 in TrkA-expressing cells results in hyperalgesia to certain stimuli, which can be reversed by simultaneous deletion of BDNF. Mechanistically, capsaicin-induced reduction of ARMS/Kidins220 leads to enhanced BDNF secretion. These findings highlight the role of ARMS/Kidins220 in the regulation of pain through the NGF/TrkA axis and BDNF secretion.
Article
Biochemistry & Molecular Biology
Paola Pacifico, Giovanna Testa, Rosy Amodeo, Marco Mainardi, Alexia Tiberi, Domenica Convertino, Juan Carlos Arevalo, Laura Marchetti, Mario Costa, Antonino Cattaneo, Simona Capsoni
Summary: A mouse model carrying the HSAN IV TrkA(R649W) mutation was successfully generated, mimicking the clinical manifestations of HSAN IV patients. The pathological R649W mutation in TrkA led to kinase-inactive TrkA and affected its membrane dynamics and trafficking. TrkA(R649W/m) mice showed reduced response to thermal and chemical noxious stimuli, decreased skin innervation, and impaired sweating, resembling the HSAN IV phenotype.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biology
Daniel Canada-Garcia, Juan C. Arevalo
Summary: Western blotting is a widely used technique for protein identification, but there is a lack of clear and common procedure for result quantification. We have developed a method based on chemiluminescent signal increase to obtain representative values for quantifying target proteins. This approach is simple and reproducible, allowing for comparison of protein levels under different conditions.
Letter
Psychiatry
Dolores Malaspina, Oded Gonen, Haley Rhodes, Kevin W. Hoffman, Adriana Heguy, Julie Walsh-Messinger, Moses V. Chao, Thorsten M. Kranz
SCHIZOPHRENIA RESEARCH
(2020)