Role of SIRT1 in autoimmune demyelination and neurodegeneration

被引:53
|
作者
Martin, Alvaro [1 ]
Tegla, Cosmin A. [1 ,2 ]
Cudrici, Cornelia D. [1 ]
Kruszewski, Adam M. [1 ]
Azimzadeh, Philippe [1 ]
Boodhoo, Dallas [1 ]
Mekala, Armugam P. [1 ]
Rus, Violeta [3 ]
Rus, Horea [1 ,2 ,4 ]
机构
[1] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA
[2] Vet Adm Maryland Hlth Care Syst, Res Serv, Baltimore, MD USA
[3] Univ Maryland, Sch Med, Dept Med, Div Rheumatol & Clin Immunol, Baltimore, MD USA
[4] Vet Adm Multiple Sclerosis Ctr Excellence, Baltimore, MD USA
关键词
SIRT1; Multiple sclerosis; Experimental allergic encephalomyelitis; Acetylation; RGC-32; Peripheral blood mononuclear cells; DEPENDENT HISTONE DEACETYLASE; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; SACCHAROMYCES-CEREVISIAE; MUTANT HUNTINGTIN; DNA-DAMAGE; TRANSCRIPTION FACTORS; AMYLOID HYPOTHESIS; PARKINSONS-DISEASE; NEGATIVE REGULATOR;
D O I
10.1007/s12026-014-8557-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:187 / 197
页数:11
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