Role of SIRT1 in autoimmune demyelination and neurodegeneration

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

doi:10.1007/s12026-014-8557-5

Cited by 54 publications

(42 citation statements)

References 122 publications

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“…In addition, studies of peripheral blood mononuclear cells (PBMCs) showed a significant decrease in SIRT1 mRNA and protein in PBMCs during relapses when compared to the levels in controls and stable MS patients. These results suggest a role for SIRT1 in MS and that modulation of SIRT1 could be a therapeutic strategy to treat MS (Martin et al, 2015; Tegla et al, 2014),…”

Section: Sirt1 – Ms and Eaementioning

confidence: 75%

SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review

Nimmagadda

Makar

Chandrasekaran

et al. 2017

Journal of Neuroimmunology

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Neurodegeneration is an important determinant of disability in multiple sclerosis (MS) but while currently approved treatments reduce inflammation, they have not been shown to reduce neurodegeneration. SIRT1, a NAD dependent protein deacetylase, has been implicated in the pathogenesis of neurodegeneration in neurological diseases including MS. We have studied the role of SIRT1 in experimental autoimmune encephalomyelitis (EAE) and found evidence for a neuroprotective role. In this review we summarize the most recent findings from the use of SIRT1 activators and SIRT1 overexpression in transgenic mice. These data support provide a rational for the use of SIRT1 activators in MS.

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Section: Sirt1 – Ms and Eaementioning

confidence: 75%

SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review

Nimmagadda

Makar

Chandrasekaran

et al. 2017

Journal of Neuroimmunology

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“…Studies have confirmed that SIRT1 is extensively expressed in tissues and organs and is associated with metabolic syndrome, tumors and neurodegenerative diseases (8)(9)(10). A previous study demonstrated that icariin exerted neuroprotective effects through the induction of SIRT1, and that these effects were reversed by the use of a SIRT1 inhibitor (11).…”

Section: Introductionmentioning

confidence: 85%

SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury via targeting p53/microRNA-22

Wang

2016

International Journal of Molecular Medicine

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Abstract. The aim of this study was to investigate whether the SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury (CIRI) via targeting p53/microRNA-22. We found that the overexpression of sirtuin 1 (SIRT1) decreased the infarct volume, suppressed p53 protein expression and activated microRNA-22 expression following CIRI. An injection of lipopolysaccharide (LPS, 1 mg/ml; Sigma, St. Louis, MO USA) into the corpus callosum was used to induce CIRI in rats. The infarct volume and neurological deficit score were used to examine the effects of SIRT1 on CIRI. Furthermore, the overexpression of SIRT1 was found to suppress caspase-3 activity, inhibit the activation of the Bax signaling pathway, reduce tumor necrosis factor-α (TNF-α) and interleukin (IL)-6) activity, decrease cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression, and increase IL-10 activity following CIRI. Following the downregulation of SIRT1, p53 protein expression was significantly increased, microRNA-22 expression was inhibited, caspase-3 activity was increased and the Bax signaling pathway was activated. In addition, the activity of TNF-α and IL-6 was was enhanced, COX-2 and iNOS protein expression was increased, and IL-10 activity was reduced following CIRI. Thus, the data from our study suggest that SIRT1 attenuates CIRI by targeting the p53/microRNA-22 axix, while suppressing apoptosis, inflammation, COX-2 and iNOS expression.

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“…In recent years, Sirt1 has emerged as a strategy for the treatment of multiple neurodegenerative disorders [25, 43–46]. Although highly expressed in the brain, Sirt1 is also known to localize in the neurons and glial cells among various cell types [47–50].…”

Section: Discussionmentioning

confidence: 99%

Interactions between Sirt1 and MAPKs regulate astrocyte activation induced by brain injury in vitro and in vivo

Liu

Zhao

et al. 2017

J Neuroinflammation

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BackgroundAstrocyte activation is a hallmark of traumatic brain injury resulting in neurological dysfunction or death for an overproduction of inflammatory cytokines and glial scar formation. Both the silent mating type information (Sirt1) expression and mitogen-activated protein kinase (MAPK) signal pathway activation represent a promising therapeutic target for several models of neurodegenerative diseases. We investigated the potential effects of Sirt1 upregulation and MAPK pathway pharmacological inhibition on astrocyte activation in vitro and in vivo. Moreover, we attempted to confirm the underlying interactions between Sirt1 and MAPK pathways in astrocyte activation after brain injury.MethodsThe present study employs an interleukin-1β (IL-1β) stimulated primary cortical astrocyte model in vitro and a nigrostriatal pathway injury model in vivo to mimic the astrocyte activation induced by traumatic brain injury. The activation of GFAP, Sirt1, and MAPK pathways were detected by Western blot; astrocyte morphological hypertrophy was assessed using immunofluorescence staining; in order to explore the neuroprotective effect of regulation Sirt1 expression and MAPK pathway activation, the motor and neurological function tests were assessed after injury.ResultsGFAP level and morphological hypertrophy of astrocytes are elevated after injury in vitro or in vivo. Furthermore, the expressions of phosphorylated extracellular regulated protein kinases (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated p38 activation (p-p38) are upregulated, but the Sirt1 expression is downregulated. Overexpression of Sirt1 significantly increases the p-ERK expression and reduces the p-JNK and p-p38 expressions. Inhibition of ERK, JNK, or p38 activation respectively with their inhibitors significantly elevated the Sirt1 expression and attenuated the astrocyte activation. Both the overproduction of Sirt1 and inhibition of ERK, JNK, or p38 activation can alleviate the astrocyte activation, thereby improving the neurobehavioral function according to the modified neurological severity scores (mNSS) and balance latency test.ConclusionsThus, Sirt1 plays a protective role against astrocyte activation, which may be associated with the regulation of the MAPK pathway activation induced by brain injury in vitro and in vivo.

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Role of SIRT1 in autoimmune demyelination and neurodegeneration

Cited by 54 publications

References 122 publications

SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review

SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review

SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury via targeting p53/microRNA-22

Interactions between Sirt1 and MAPKs regulate astrocyte activation induced by brain injury in vitro and in vivo

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