Review
Neurosciences
Davin Packer, Emily. E. E. Fresenko, Em. P. P. Harrington
Summary: Significant progress has been made in understanding the biology of remyelination and its potential as a therapeutic strategy for preventing neurodegeneration and disability in multiple sclerosis (MS). Different animal models have been used to study oligodendroglial responses and remyelination, each with its own mechanisms of demyelination, involvement of inflammatory cells, neurodegeneration, and capacity for remyelination. It is important to investigate remyelination in the context of aging and an inflammatory environment for potential translation to progressive MS. This review discusses the assessment of remyelination in mouse models of demyelination, the differences and advantages of these models, emerging therapeutic strategies, and current clinical trials promoting remyelination.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
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)
Review
Neurosciences
Karina Maciak, Angela Dziedzic, Joanna Saluk
Summary: Remyelination depends on the repair of damaged myelin sheaths, involving microglia cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes. Short, noncoding RNA molecules, microRNAs (miRNAs), are believed to play a crucial role in the remyelination process by regulating gene expression. Various delivery systems, including extracellular vesicles, hold promise as an efficient and non-invasive way for providing miRNAs to stimulate remyelination.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Ana Palma, Juan Carlos Chara, Alejandro Montilla, Amaia Otxoa-de-Amezaga, Francisca Ruiz-Jaen, Anna M. Planas, Carlos Matute, Alberto Perez-Samartin, Maria Domercq
Summary: Abnormalities in myelination are associated with behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Clemastine, a drug that promotes myelination, has complex effects on myelin development during the developmental process. The study found that clemastine treatment increased oligodendrocyte differentiation but decreased conduction velocity and myelin thickness in the corpus callosum. Additionally, the population of microglia cells and insulin growth factor-1 levels decreased in clemastine-treated mice.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Neurosciences
Mohanlall Narine, Holly Colognato
Summary: Oligodendroglial cells play important roles in neurological functions such as myelination, neuroprotection, and motor learning. Recent studies have focused on understanding the role of oligodendroglial metabolism in regulating cell development, energy supply to neighboring cells, and its contribution to disease states. Inputs such as cellular signaling, pharmacological compounds, and dietary interventions can regulate oligodendroglial metabolism. Targeting components within oligodendroglial bioenergetic pathways may have therapeutic potential.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Christian Cordano, Jung H. Sin, Garrett Timmons, Hao H. Yiu, Karin Stebbins, Caroline Guglielmetti, Andres Cruz-Herranz, Wendy Xin, Daniel Lorrain, Jonah R. Chan, Ari J. Green
Summary: Many biomarkers in clinical neuroscience lack pathological certification, which hinders the success of neuroprotective and neurorestorative therapies. In the field of myelin repair, validated methods to demonstrate therapeutic efficacy or provide preclinical evidence of remyelination are lacking. Visual evoked potentials have shown potential as a biomarker for remyelination, but further evidence is needed to support its use. This study validates the use of visual evoked potentials as a preclinical biomarker of remyelination efficacy.
Article
Neurosciences
Tal Ganz, Omri Zveik, Nina Fainstein, Marva Lachish, Ariel Rechtman, Lihi Sofer, Livnat Brill, Tamir Ben-Hur, Adi Vaknin-Dembinsky
Summary: Pushing OPC into differentiation program may help overcome remyelination failure, but creating a permissive environment for OPC activation, migration, and differentiation is also crucial.
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)
Article
Neurosciences
Omri Zveik, Nina Fainstein, Ariel Rechtman, Nitzan Haham, Tal Ganz, Iris Lavon, Livnat Brill, Adi Vaknin-Dembinsky
Summary: Oligodendrocyte progenitor cells play a role in both remyelination and immune response in the central nervous system. CSF from patients with progressive MS impairs differentiation of OPCs and reduces immune functions.
Review
Biochemistry & Molecular Biology
Ilias Kalafatakis, Domna Karagogeos
Summary: This review summarizes the regulation of myelination by oligodendrocytes under physiological and pathological conditions, as well as the role of microglia in myelin generation, regeneration, and repair. The beneficial and detrimental roles of microglia in remyelination are discussed, along with the cellular and molecular components involved. Recent findings related to preclinical models using human stem cells for studying microglia in human pathologies and the impact of the microbiome on glial cell functions are also presented.
Article
Neurosciences
James J. M. Cooper, Jessie J. Polanco, Darpan Saraswat, Jennifer J. Peirick, Anna Seidl, Yi Li, Dan Ma, Fraser J. Sim
Summary: The failure of remyelination in the human CNS is a major contributor to axonal injury and disease progression in multiple sclerosis (MS). Murine models show a high density of oligodendrocyte progenitor cells (OPCs) in areas of demyelination, suggesting that efficient OPC repopulation is necessary for successful remyelination. However, in this study, we found that OPC repopulation was low in large lesions and almost absent in small lesions in adult rabbits, suggesting that both lesion volume and species-specific mechanisms play a role in regulating OPC proliferation and remyelination.
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.
Review
Pharmacology & Pharmacy
Rujapope Sutiwisesak, Terry C. Burns, Moses Rodriguez, Arthur E. Warrington
Summary: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS) characterized by demyelination. Remyelination, the natural repair process, eventually fails in most patients. Development of therapeutics for remyelination needs to take into account the heterogeneity of human MS, since some patients lack the necessary biological targets for current approaches.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Review
Pharmacology & Pharmacy
Jennifer Cadenas-Fernandez, Pablo Ahumada-Pascual, Luis Sanz Andreu, Ana Velasco
Summary: Multiple sclerosis (MS) is an autoimmune and inflammatory central nervous system disease with no effective treatments currently available. One of the main research goals is to find therapies that can promote the recovery of neurological disabilities caused by demyelination. This study reviews a variety of drugs that may promote endogenous remyelination in MS patients and could be potential therapeutic agents for the disease.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Neurosciences
Shuang-Ling Wu, Bin Yu, Yong-Jie Cheng, Shu-Yu Ren, Fei Wang, Lan Xiao, Jing-Fei Chen, Feng Mei
Summary: Alzheimer's disease (AD) is characterized by the presence of aggregated amyloid beta-protein (Aβ). Recent evidence suggests that inadequate myelinogenesis plays a role in AD-related functional deficits. The relationship between Aβ and myelinogenesis in AD brains, however, remains unclear.
EXPERIMENTAL NEUROLOGY
(2023)