SIRT1 mRNA expression appears to be downregulated in peripheral blood mononuclear cells (PBMCs) in patients with acute neuromyelitis optica spectrum disorder (NMOSD) attacks, but more research is required to assess its role in the pathogenesis of the disease, according to a recently published study in Acta Neurologica Belgica.
SIRT1 belongs to the family of histone deacetylases (HDACs), specifically HDACIII, which includes 7 members with distinct functions. It is located in the cellular nucleus and has important immunomodulatory functions, impacting the generation and differentiation of immune cells and inhibiting inflammation through multiple pathways.
Although SIRT1 has been shown to play a role in animal models of some demyelinating and neurodegenerative diseases, its role in NMOSD is unclear.
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The authors used real-time fluorescence quantitative-polymerase chain reaction to detect SIRT1 mRNA levels in 65 patients with NMOSD, of which 43 were in an acute phase, and 60 healthy controls. Western blot was used to determine SIRT1 protein levels in the same population.
Read more about NMOSD etiology
Results showed SIRT1 mRNA levels to be significantly decreased in patients with NMOSD, compared to healthy controls. The authors observed that mRNA levels were lower in the acute phase NMOSD group than in chronic patients. SIRT1 mRNA was directly correlated to mononuclear cell counts and inversely correlated with neutrophil counts.
Regarding clinical correlation with SIRT1 mRNA, the authors reported that although there was no significant correlation between mRNA levels and Expanded Disability Status Scale (EDSS) score, there was a noteworthy correlation between mRNA levels and the difference between EDSS scores in the acute phase and EDSS scores before the recent attack, which were used as a measure of attack severity.
Measurements of inflammatory factors and cytokines showed no statistically significant correlation with SIRT1 levels.
“Our study demonstrated that SIRT1 expression was decreased in the PBMCs of patients with acute-phase NMOSD, and it might be associated with the clinical characteristics and may be involved in NMOSD pathogenesis,” the authors wrote.
The authors recognized that more research is required to accurately assess the value of SIRT1 in NMOSD pathogenesis.
Reference
Zhang L, Xue Y, Yuan C, et al. Decreased SIRT1 mRNA expression in peripheral blood mononuclear cells from patients with neuromyelitis optica spectrum disorders. Acta Neurol Belg. Published online June 9, 2023. doi:10.1007/s13760-023-02300-3
