Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells

Mi, Sha; Miller, Robert H.; Tang, Wei; Lee, Xinhua; Hu, Bing; Wu, Wutain; Zhang, Yiping; Shields, Christopher B.; Zhang, Yongjie; Miklasz, Steven D.; Shea, Diana; Mason, Jeffrey L.; Franklin, Robin J.M.; Ji, Benxiu; Shao, Zhaohui; Chédotal, Alain; Bernard, Frédéric; Roulois, Aude; Xu, Janfeng; Jung, Vincent; Pepinsky, Blake

doi:10.1002/ana.21581

Cited by 276 publications

(206 citation statements)

References 28 publications

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“…On the other hand, LINGO-1-deficient mice or mice treated with an anti-LINGO-1 antibody exhibited greater remyelination and functional recovery when submitted to EAE (Mi et al 2007). The same observations were made when animals were submitted to toxin-induced demyelination (Mi et al 2009). As for the Wnt signaling pathway, Fancy et al (2009) identified pathway-associated genes that are induced during remyelination in mice submitted to experimental demyelination.…”

Section: Underlying Mechanisms In Demyelination/ Remyelination Processessupporting

confidence: 53%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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Demyelination is a pathological process characterized by the loss of myelin around axons. In the central nervous system, oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Remyelination is a regenerative process by which myelin sheaths are restored to demyelinated axons, resolving functional deficits. This process is often deficient in demyelinating diseases such as multiple sclerosis (MS), and the reasons for the failure of repair mechanisms remain unclear. The characterization of these mechanisms and the factors involved in the proliferation, recruitment, and differentiation of oligodendroglial progenitor cells is key in designing strategies to improve remyelination in demyelinating disorders. First, a very dynamic combination of different molecules such as growth factors, cytokines, chemokines, and different signaling pathways is tightly regulated during the remyelination process. Second, factors unrelated to this pathology, i.e., age and genetic background, may impact disease progression either positively or negatively, and in particular, age-related remyelination failure has been proven to involve oligodendroglial cells aging and their intrinsic capacities among other factors. Third, nutrients may either help or hinder disease progression. Experimental evidence supports the anti-inflammatory role of omega-6 and omega-3 polyunsaturated fatty acids through the competitive inhibition of arachidonic acid, whose metabolites participate in inflammation, and the reduction in T cell proliferation. In turn, vitamin D intake and synthesis have been associated with lower MS incidence levels, while vitamin D-gene interactions might be involved in the pathogenesis of MS. Finally, dietary polyphenols have been reported to mitigate demyelination by modulating the immune response.

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Section: Underlying Mechanisms In Demyelination/ Remyelination Processessupporting

confidence: 53%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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“…Mice deficient in LINGO-1 or treated with an antibody antagonist against LINGO-1 exhibited increased remyelination and functional recovery from EAE, a model of immune-mediated demyelination [53]. Moreover, the LINGO-1 antagonist is able to promote CNS remyelination by directly stimulating OPC differentiation in nonimmune, toxin-induced models of demyelination in rats [54]. These findings reveal the importance of LINGO-1 signaling in regulating OPC differentiation in the injured CNS.…”

Section: Pharmacological Targets Of Remyelinationmentioning

confidence: 79%

Myelin Regeneration in Multiple Sclerosis: Targeting Endogenous Stem Cells

et al. 2011

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Regeneration of myelin sheaths (remyelination) after central nervous system demyelination is important to restore saltatory conduction and to prevent axonal loss. In multiple sclerosis, the insufficiency of remyelination leads to the irreversible degeneration of axons and correlated clinical decline. Therefore, a regenerative strategy to encourage remyelination may protect axons and improve symptoms in multiple sclerosis. We highlight recent studies on factors that influence endogenous remyelination and potential promising pharmacological targets that may be considered for enhancing central nervous system remyelination.

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“…Attenuation of LiNGo-1 function in oPCs by siRNA, dominant-negative LiNGo-1, LiNGo-1-Fc or LiNGo knockout, invariably promotes oPC differentiation and myelination in vitro [48][49][50][51] . Blockade of LiNGo-1 signaling promotes myelination in oPC-DRG co-cultures and LPC-treated cerebellar slice cultures [50,52] .…”

Section: Lingo-1mentioning

confidence: 99%

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

Zhang

Guo

2013

Neurosci. Bull.

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Multiple sclerosis (MS) is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.

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Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells

Abstract: Our studies demonstrate that LINGO-1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO-1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination.

Cited by 276 publications

References 28 publications

Nutritional factors and aging in demyelinating diseases

Nutritional factors and aging in demyelinating diseases

Myelin Regeneration in Multiple Sclerosis: Targeting Endogenous Stem Cells

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

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