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Role of SIRT1 in autoimmune demyelination and neurodegeneration

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Abstract

Multiple sclerosis (MS) is a demyelinating disease characterized by chronic inflammation of the central nervous system, in which many factors can act together to influence disease susceptibility and progression. SIRT1 is a member of the histone deacetylase class III family of proteins and is an NAD+-dependent histone and protein deacetylase. SIRT1 can induce chromatin silencing through the deacetylation of histones and plays an important role as a key regulator of a wide variety of cellular and physiological processes including DNA damage, cell survival, metabolism, aging, and neurodegeneration. It has gained a lot of attention recently because many studies in animal models of demyelinating and neurodegenerative diseases have shown that SIRT1 induction can ameliorate the course of the disease. SIRT1 expression was found to be decreased in the peripheral blood mononuclear cells of MS patients during relapses. SIRT1 represents a possible biomarker of relapses and a potential new target for therapeutic intervention in MS. Modulation of SIRT1 may be a valuable strategy for treating or preventing MS and neurodegenerative central nervous system disorders.

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Acknowledgments

We thank Dr. Deborah McClellan for editing this manuscript. This work was supported in part by a Pilot Project PP 1422 from the MS Society (to H. R.) and a Veterans Administration Merit Award (BX 001458 to H. R.). The MS brain samples were obtained from the National Neurological Research Specimen Bank (West Los Angeles Veterans Administration Hospital, Los Angeles, CA).

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Authors and Affiliations

  1. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Alvaro Martin, Cosmin A. Tegla, Cornelia D. Cudrici, Adam M. Kruszewski, Philippe Azimzadeh, Dallas Boodhoo, Armugam P. Mekala & Horea Rus

  2. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Violeta Rus

  3. Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA

    Cosmin A. Tegla & Horea Rus

  4. Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD, USA

    Horea Rus

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  1. Alvaro Martin
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  2. Cosmin A. Tegla
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  8. Violeta Rus
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Correspondence to Horea Rus.

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Martin, A., Tegla, C.A., Cudrici, C.D. et al. Role of SIRT1 in autoimmune demyelination and neurodegeneration. Immunol Res 61, 187–197 (2015). https://doi.org/10.1007/s12026-014-8557-5

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