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

Foolad, Forough; Khodagholi, Fariba; Javan, Mohammad

doi:10.1016/j.msard.2019.06.004

Cited by 22 publications

(17 citation statements)

References 176 publications

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“…Moreover, sirtuins have a wide range of effects on BBB integrity, apoptosis, and excitotoxicity in other in vivo and in vitro models of brain injury. As a result of these pleiotropic effects, sirtuins have been acknowledged to be emerging targets for TBI and TBI-related neurodegeneration (Donmez and Outeiro, 2013;Foolad et al, 2019).…”

Section: Sirtuins As Promising Therapeutic Targetsmentioning

confidence: 99%

Will Sirtuins Be Promising Therapeutic Targets for TBI and Associated Neurodegenerative Diseases?

et al. 2020

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Traumatic brain injury (TBI), a leading cause of morbidity worldwide, induces mechanical, persistent structural, and metabolic abnormalities in neurons and other brain-resident cells. The key pathological features of TBI include neuroinflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. These pathological processes persist for a period of time after TBIs. Sirtuins are evolutionarily conserved nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylases and mono-ADP-ribosyl transferases. The mammalian sirtuin family has seven members, referred to as Sirtuin (SIRT) 1-7. Accumulating evidence suggests that SIRT1 and SIRT3 play a neuroprotective role in TBI. Although the evidence is scant, considering the involvement of SIRT2, 4-7 in other brain injury models, they may also intervene in similar pathophysiology in TBI. Neurodegenerative diseases are generally accepted sequelae of TBI. It was found that TBI and neurodegenerative diseases have many similarities and overlaps in pathological features. Besides, sirtuins play some unique roles in some neurodegenerative diseases. Therefore, we propose that sirtuins might be a promising therapeutic target for both TBI and associated neurodegenerative diseases. In this paper, we review the neuroprotective effects of sirtuins on TBI as well as related neurodegeneration and discuss the therapeutic potential of sirtuin modulators.

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Section: Sirtuins As Promising Therapeutic Targetsmentioning

confidence: 99%

Will Sirtuins Be Promising Therapeutic Targets for TBI and Associated Neurodegenerative Diseases?

et al. 2020

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“…In this study, to investigate the relationship between the systemic metabolic and NMO severity; we evaluated the activity of mitochondrial complex I and IV, and also aconitase and α-ketoglutarate dehydrogenase (α-KGD) as important enzymes to energy production in PBMCs of NMO patients. Moreover, we measured the level of sirtuin 1 (SIRT1) and 3 in PBMCs and SIRT1 in plasma due to their critical roles in the physiology of central nervous system, immune system and metabolism [17] and long term changes in gene expression via their epigenetic modifying role. In addition plasma level of pyruvate and lactate was determined to show aerobic/nonaerobic metabolism ratio of CNS, and cytochrome c (Cyt c) level as a marker of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Changes in mitochondrial function in patients with neuromyelitis optica; correlations with motor and cognitive disabilities

et al. 2020

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Background Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease that mainly affects optic nerves and spinal cord. Besides, loss of motor and cognitive function has been reported as important symptoms of disease. Objective Here we investigated the mitochondrial dysfunction and metabolic alterations in NMO patients and evaluate their correlation with disease progress, disability and cognitive impairment. Methods The individuals (12 controls and 12 NMO) were assessed for disease severity by expanded disease status scale (EDSS), cognitive function via symbol digit modalities test (SDMT) and fine motor disability by 9-hole peg test (9-HPT). We have measured Sirtuin 1 (SIRT1), SIRT3, mitochondrial complex I, complex IV, aconitase and α-ketoglutarate dehydrogenase (α-KGD) activity in peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate and cytochrome c (Cyt c) were determined in plasma. Results Our results exhibited increased 9-HPT time in NMO patients. 9-HPT results correlated with EDSS; and SDMT negatively correlated with disease duration and number of attacks in patients. Investigation of PBMCs of NMO patients exhibited a decrease of mitochondrial complex I and IV activity that was significant for complex IV. Besides, complex I activity was negatively correlated with 9-HPT time in NMO group. In the plasma samples, a correlation between pyruvate to lactate ratio and EDSS in NMO patients was found and a negative correlation between Cyt c concentration and SDMT was detected.

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“…These results suggest that sirtuins, as NAD + sensors, might also be involved in this process. Besides their role in sepsis, sirtuins may also be involved in other inflammatory-mediated conditions (as discussed below) and have been proposed as potential targets for novel therapies for the treatment of autoimmune diseases and leukemias [57,99].…”

Section: Sirtuins At the Crossroad Of Metabolism And Immune-related Diseasesmentioning

confidence: 99%

“…Thus, the regulation of immunometabolism is essential in the development and progression of these pathological conditions, and sirtuins, as modulators of cellular metabolism, could play important roles on this. Indeed, some studies have shown that sirtuins are involved in systemic lupus erythematosus and MS [99,102], al-though the precise mechanism by which they regulate the progression of these diseases is not fully understood.…”

Section: Sirtuins At the Crossroad Of Metabolism And Immune-related Diseasesmentioning

confidence: 99%

Sirtuins as Metabolic Regulators of Immune Cells Phenotype and Function

Fortuny

Sebastián

2021

Genes

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Beyond its role on the conversion of nutrients into energy and biomass, cellular metabolism is actively involved in the control of many physiological processes. Among these, it is becoming increasingly evident that specific metabolic pathways are associated with the phenotype of several immune cell types and, importantly, are crucial in controlling their differentiation, proliferation, and effector functions, thus shaping the immune response against pathogens and tumors. In this context, data generated over the last decade have uncovered mammalian sirtuins as important regulators of cellular metabolism, immune cell function, and cancer. Here, we summarize our current knowledge on the roles of this family of protein deacylases on the metabolic control of immune cells and their implications on immune-related diseases and cancer.

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

Cited by 22 publications

References 176 publications

Will Sirtuins Be Promising Therapeutic Targets for TBI and Associated Neurodegenerative Diseases?

Will Sirtuins Be Promising Therapeutic Targets for TBI and Associated Neurodegenerative Diseases?

Changes in mitochondrial function in patients with neuromyelitis optica; correlations with motor and cognitive disabilities

Sirtuins as Metabolic Regulators of Immune Cells Phenotype and Function

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