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Oxidative Stress in Multiple Sclerosis Pathology and Therapeutic Potential of Nrf2 Activation

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Book cover Oxidative Stress and Free Radical Damage in Neurology

Abstract

Reactive oxygen species contribute to the formation and persistence of multiple sclerosis (MS) lesions by acting on distinct pathological processes. To counteract the detrimental effects of reactive oxygen species, the central nervous system is endowed with a protective mechanism consisting of enzymatic and nonenzymatic antioxidants. Expression of most antioxidant enzymes is regulated through the transcription factor nuclear factor-E2-related factor (Nrf2), and antioxidant response elements (ARE) in the genes encoding enzymatic antioxidants and are induced by oxidative stress. In brain tissue of MS patients, enhanced expression of Nrf2/ARE-regulated antioxidants suggests the occurrence of oxidative stress in these lesions. Antioxidant therapy may therefore represent an attractive treatment of MS. Several studies have shown that antioxidant therapy is beneficial in vitro and in vivo in animal models for MS. However, the use of exogenous antioxidants for MS treatment has drawbacks, as large amounts of antioxidants are required to achieve functional antioxidant levels in the central nervous system. Therefore, the induction of endogenous antioxidant enzymes by activators of the Nrf2/ARE pathway may be an interesting approach to obtain sufficient levels of antioxidants to interfere with pathological processes underlying MS lesion formation. Here we discuss and summarize the biological role, regulation, and potential therapeutic effects of endogenous antioxidant enzymes in MS.

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Acknowledgments

This work was supported by grants from “The Dutch Foundation of MS Research,” The Netherlands (project numbers 05–567 MS and 05–358c MS (J. van Horssen) and MS 02–358 (H.E. de Vries), and the Institute for Clinical and Experimental Neurosciences, VU University Medical Center, Amsterdam, The Netherlands (G. Schreibelt).

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  1. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands

    Jack van Horssen

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  1. Helga E. de Vries
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  2. Gerty Schreibelt
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  3. Jack van Horssen
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Correspondence to Jack van Horssen .

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Editors and Affiliations

  1. Medical School, Dept. Neurology, Tel Aviv University, Tel Aviv, 69978, Israel

    Natan Gadoth

  2. Neurochirurgische Klinik, Abt. Neuropathologie, Universitätsklinikum Mainz, Langenbeckstr. 1, Mainz, 55131, Germany

    Hans Hilmar Göbel

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de Vries, H.E., Schreibelt, G., van Horssen, J. (2011). Oxidative Stress in Multiple Sclerosis Pathology and Therapeutic Potential of Nrf2 Activation. In: Gadoth, N., Göbel, H. (eds) Oxidative Stress and Free Radical Damage in Neurology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-60327-514-9_5

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