SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis

Hewes, Daniel; Tatomir, Alexandru; Kruszewski, Adam M.; Rao, Gautam; Tegla, Cosmin; Ciriello, Jonathan; Nguyen, Vingh; Royal, Walter; Rus, Violeta; Rus, Horea

doi:10.1016/j.yexmp.2017.01.014

Cited by 29 publications

(20 citation statements)

References 32 publications

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“…Peripheral blood mononuclear cells (PBMCs) have been an important target for studies. Several studies demonstrated SIRT1 as a biomarker and reported that expression of this molecule in PBMCs obtained from MS patients in the relapse phase was decreased compared to healthy controls and patient with stable MS (Ciriello et al, 2018;Hewes et al, 2017;Tegla et al, 2014). Tegla and colleagues also showed the elevated expression of SIRT1 in acute and chronic lesion sites when compared to normal brain tissue.…”

Section: Sirt7 Knockoutmentioning

confidence: 98%

“…Human-MS Decrease of SIRT1 expression in PBMCs in Relapse phase (Ciriello et al, 2018;Hewes et al, 2017;Tegla et al, 2014) Human-MS Increase of SIRT1 expression in acute and chronic lesion sites (Tegla et al, 2014) Human-MS Increase of SIRT1 level in plasma samples (Pennisi et al, 2011) SIRT2 Wistar rats RNA knockdown of SIRT2 Increase of tubulin acetylation, MBP expression, and cell arbor complexity of OPCs (Li et al, 2007) Human-MS Presence of antibodies against SIRT2 in the CSF (Lovato et al, 2008) EAE mouse Decrease in the level of SIRT2 (Jastorff et al, 2009) EAE mouse Increase in level of transcription of SIRT2 in the CNS during chronic disease stages (Prozorovski et al, 2019) Human-MS Decrease in level of several isoform of SIRT2 in MS lesions (Jastorff et al, 2009) SIRT3 Human-MS Reduction in the level of SIRT3 expression in MS affected brain (Rice et al, 2012) SIRT4 Human-MS Change in genetic variants (Inkster et al, 2013) SIRT5 Human-MS Change in genetic variants (Inkster et al, 2013) SIRT6 EAE mouse Increase in level of transcription of SIRT6 in the CNS during chronic disease stages (Prozorovski et al, 2019) SIRT7 EAE mouse…”

Section: Sirtuin-1mentioning

confidence: 99%

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Sirtuins in Multiple Sclerosis: The crossroad of neurodegeneration, autoimmunity and metabolism

Foolad

Khodagholi

Javan

2019

Multiple Sclerosis and Related Disorders

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Section: Sirt7 Knockoutmentioning

confidence: 98%

Section: Sirtuin-1mentioning

confidence: 99%

Sirtuins in Multiple Sclerosis: The crossroad of neurodegeneration, autoimmunity and metabolism

Foolad

Khodagholi

Javan

2019

Multiple Sclerosis and Related Disorders

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“…On the contrary, another group found that silencing Sirt1 can ameliorate remyelination in lysolecithin‐induced demyelination model, and delay onset of paralysis in EAE models (Rafalski et al., ). Although these inconsistent contribution of SIRT1 in demyelination remains to be finally determined, current studies indicate that SIRT1 might be a biomarker of relapses and a potential target for therapeutic intervention in MS (Hewes et al., ; Tegla et al., ).…”

Section: The Role Of Histone Deacetylase (Hdac) Family In Oligodendromentioning

confidence: 99%

Epigenetic regulation of myelination in health and disease

Zhang

Wang

et al. 2019

Eur J of Neuroscience

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Myelin is lipid‐rich structure that is necessary to avoid leakage of electric signals and to ensure saltatory impulse conduction along axons. Oligodendrocytes in central nervous system (CNS) and Schwann cells in peripheral nervous system (PNS) are responsible for myelin formation. Axonal demyelination after injury or diseases greatly impairs normal nervous system function. Therefore, understanding how the myelination process is programmed, coordinated, and maintained is crucial for developing therapeutic strategies for remyelination in the nervous system. Epigenetic mechanisms have been recognized as a fundamental contributor in this process. In recent years, histone modification, DNA modification, ATP‐dependent chromatin remodeling, and non‐coding RNA modulation are very active area of investigation. We will present a conceptual framework that integrates crucial epigenetic mechanisms with the regulation of oligodendrocyte and Schwann cell lineage progression during development and myelin degeneration in pathological conditions. It is anticipated that a refined understanding of the molecular basis of myelination will aid in the development of treatment strategies for debilitating disorders that involve demyelination, such as multiple sclerosis in the CNS and neuropathies in the PNS.

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“…SIRT1 is a NAD-dependent class III histone deacetylase (HDAC) involved in the regulation of transcription, apoptosis, metabolism, and differentiation. It catalyzes the removal of acetyl groups from a variety of protein substrates and promotes histone H3 lysine 9 (H3K9) methylation, contributing to heterochromatin formation and transcription silencing (14,15). We have found that SIRT1 is co-localized with surviving OLGs in MS plaques and is also expressed by astrocytes and CD4and CD68-positive cells in MS brains (16).…”

Section: Introductionmentioning

confidence: 99%

“…We have found that SIRT1 is co-localized with surviving OLGs in MS plaques and is also expressed by astrocytes and CD4and CD68-positive cells in MS brains (16). We have also shown that SIRT1 expression is reduced in peripheral blood Abbreviations: CNS, central nervous system; CSPG4, chondroitin sulfate proteoglycan 4; EAE, experimental autoimmune encephalomyelitis; ERK, extracellular-regulated kinase; MBP, myelin basic protein; MS, multiple sclerosis; NG2, neuron glial antigen 2; OLG, oligodendrocyte; OPC, oligodendrocyte precursor cell; PI3K, phosphoinositide 3-kinase; PKC, protein kinase C; PLP, proteolipid protein; p-SIRT1, phosphorylated SIRT1; SIRT1, sirtuin 1. mononuclear cells of MS patients during relapses and in those who do not respond to treatment with glatiramer acetate, a disease-modifying drug used for treating MS, suggesting that SIRT1 could serve as a biomarker of disease activity and patient responsiveness to therapy (15,17). Other studies have indicated that SIRT1 is involved in OPCs proliferation and differentiation toward OLGs during pathological conditions (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Histone Deacetylase SIRT1 Mediates C5b-9-Induced Cell Cycle in Oligodendrocytes

et al. 2020

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Sublytic levels of C5b-9 increase the survival of oligodendrocytes (OLGs) and induce the cell cycle. We have previously observed that SIRT1 co-localizes with surviving OLGs in multiple sclerosis (MS) plaques, but it is not yet known whether SIRT1 is involved in OLGs survival after exposure to sublytic C5b-9. We have now investigated the role of SIRT1 in OLGs differentiation and the effect of sublytic levels of C5b-9 on SIRT1 and phosphorylated-SIRT1 (Ser27) expression. We also examined the downstream effects of SIRT1 by measuring histone H3 lysine 9 trimethylation (H3K9me3) and the expression of cyclin D1 as a marker of cell cycle activation. OLG progenitor cells (OPCs) purified from the brain of rat pups were differentiated in vitro and treated with sublytic C5b-9 or C5b6. To investigate the signaling pathway activated by C5b-9 and required for SIRT1 expression, we pretreated OLGs with a c-jun antisense oligonucleotide, a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002), and a protein kinase C (PKC) inhibitor (H7). Our data show a significant reduction in phospho-SIRT1 and SIRT1 expression during OPCs differentiation, associated with a decrease in H3K9me3 and a peak of cyclin D1 expression in the first 24 h. Stimulation of OLGs with sublytic C5b-9 resulted in an increase in the expression of SIRT1 and phospho-SIRT1, H3K9me3, cyclin D1 and decreased expression of myelin-specific genes. C5b-9-stimulated SIRT1 expression was significantly reduced after pretreatment with c-jun antisense oligonucleotide, H7 or LY294002. Inhibition of SIRT1 with sirtinol also abolished C5b-9-induced DNA synthesis. Taken together, these data show that induction of SIRT1 expression by C5b-9 is required for cell cycle activation and is mediated through multiple signaling pathways.

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SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis

Cited by 29 publications

References 32 publications

Sirtuins in Multiple Sclerosis: The crossroad of neurodegeneration, autoimmunity and metabolism

Sirtuins in Multiple Sclerosis: The crossroad of neurodegeneration, autoimmunity and metabolism

Epigenetic regulation of myelination in health and disease

Histone Deacetylase SIRT1 Mediates C5b-9-Induced Cell Cycle in Oligodendrocytes

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