Article
Multidisciplinary Sciences
Simone Patergnani, Massimo Bonora, Selene Ingusci, Maurizio Previati, Saverio Marchi, Silvia Zucchini, Mariasole Perrone, Mariusz R. Wieckowski, Massimiliano Castellazzi, Maura Pugliatti, Carlotta Giorgi, Michele Simonato, Paolo Pinton
Summary: The study found that autophagy and mitophagy are increased in MS patients, with inhibitors of autophagy improving myelination and behavioral signs in experimental models of the disease, suggesting a causal role of autophagy in MS and potential therapeutic benefits of autophagy inhibitors like haloperidol and clozapine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Clinical Neurology
Samira Ghorbani, V. Wee Yong
Summary: Failure of remyelination in multiple sclerosis lesions is influenced by changes in extracellular matrix components, which not only impair oligodendrocyte recruitment but also enhance inflammatory responses. The deposition of matrix members is mainly due to cells such as reactive astrocytes and microglia/macrophages, leading to both pro-inflammatory and anti-inflammatory effects within the lesions.
Article
Immunology
Melissa Schepers, Dean Paes, Assia Tiane, Ben Rombaut, Elisabeth Piccart, Lieve van Veggel, Pascal Gervois, Esther Wolfs, Ivo Lambrichts, Chiara Brullo, Olga Bruno, Ernesto Fedele, Roberta Ricciarelli, Charles Ffrench-Constant, Marie E. Bechler, Pauline van Schaik, Wia Baron, Evy Lefevere, Kobi Wasner, Anne Grunewald, Catherine Verfaillie, Paulien Baeten, Bieke Broux, Paul Wieringa, Niels Hellings, Jos Prickaerts, Tim Vanmierlo
Summary: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by central nervous system inflammation and demyelination. Current therapies are insufficient in halting or reversing disease progression. This study shows that selective inhibition of phosphodiesterase 4 (PDE4) promotes myelin repair and reduces inflammation. Inhibition of PDE4D enhances (re)myelination, while inhibition of PDE4B exerts anti-inflammatory effects. These findings suggest that gene specific PDE4 inhibitors could be potential therapeutic agents for MS.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Cell Biology
Mansour Haidar, Melanie Loix, Sam Vanherle, Tess Dierckx, Tim Vangansewinkel, Pascal Gervois, Esther Wolfs, Ivo Lambrichts, Jeroen F. J. Bogie, Jerome J. A. Hendriks
Summary: Foamy macrophages containing myelin remnants are a hallmark of multiple sclerosis. Accumulation of myelin-derived lipids in these macrophages promotes inflammation. Disturbed lipophagy, a form of autophagy, contributes to this inflammatory phenotype. Stimulating autophagy with trehalose reduces lipid load and inflammation in myelin-laden macrophages and promotes remyelination in models of demyelination. These findings suggest that targeting lipophagy may be a promising treatment strategy for promoting remyelination in multiple sclerosis.
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
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
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
Biology
Nadjet Gacem, Brahim Nait-Oumesmar
Summary: Myelination by oligodendrocytes is crucial for central nervous system development and function, with multiple sclerosis being a common neurodegenerative disease characterized by inflammation and demyelination. Current treatments for MS target the immune component of the disease, but there is ongoing research on pharmacological compounds that could enhance remyelination.
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
Laura Ghezzi, Bryan Bollman, Luca De Feo, Laura Piccio, Bruce D. Trapp, Robert E. Schmidt, Anne H. Cross
Summary: Multiple sclerosis (MS) is a CNS demyelinating disease that often leads to unsuccessful remyelination and neuronal/axonal damage. While oligodendroglial cells are responsible for myelin production, remyelination by Schwann cells (SchC) has been observed in spinal cord demyelination. This study investigated the extent of SchC remyelination in the brain and spinal cords of autopsied MS specimens.
LABORATORY INVESTIGATION
(2023)
Review
Clinical Neurology
Vanja Tepavcevi, Catherine Lubetzki
Summary: The failure of remyelination in multiple sclerosis (MS) is often characterized by low oligodendrocyte progenitor cell density. Stimulating this process may be crucial for achieving myelin regeneration.
Article
Neurosciences
Li-Hsin Huang, Zih-Yun Pan, Yi-Ju Pan, Feng-Yi Yang
Summary: This study investigated the ability of transcranial ultrasound stimulation (TUS) to promote remyelination in the hippocampus. The findings showed that TUS can attenuate the myelin loss and reduce the size of demyelinated lesions. The results suggest that MTR is a sensitive and reproducible quantitative marker for assessing the remyelination process during TUS treatment.
Article
Biochemistry & Molecular Biology
Marije J. D. Huitema, Eva M. M. Strijbis, Antonio Luchicchi, John G. J. M. Bol, Jason R. Plemel, Jeroen J. G. Geurts, Geert J. Schenk
Summary: Multiple sclerosis is a demyelinating and neurodegenerative disease of the central nervous system. This study introduced and validated a novel standardized method for more precise myelin quantification in progressive MS brains. The method showed excellent inter-rater agreement and reliability in quantifying myelin content in human post-mortem samples.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Vanessa Wiggermann, Verena Endmayr, Enedino Hernandez-Torres, Romana Hoeftberger, Gregor Kasprian, Simon Hametner, Alexander Rauscher
Summary: Magnetic resonance imaging (MRI) can provide important insights into multiple sclerosis (MS) by detecting focal or diffuse myelin damage or remyelination. This study used three myelin-sensitive MRI scans and histopathological measurements to evaluate the different stages of MS pathology, including chronic demyelinated and remyelinated lesions. The results showed that inactive lesions in chronic MS cases had increased myelin densities, indicating low-level remyelination.
Review
Clinical Neurology
Catherine Lubetzki, Bernard Zalc, David Kremer, Patrick Kuery
Summary: Recent research has shown that the human brain has the ability to self-regenerate demyelinated lesions, opening up possibilities for repairing and protecting nerve fibers in multiple sclerosis patients. This review discusses the mechanisms involved in the remyelination process and provides an update on current strategies for promoting endogenous myelin repair.
CURRENT OPINION IN NEUROLOGY
(2022)