Roles of sirtuins in asthma

Abstract

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases and deacetylases that participate in a variety of cellular processes, including transcriptional activity, energy metabolism, DNA damage response, inflammation, apoptosis, autophagy, and oxidative stress. As a result, sirtuins are linked to multiple pathophysiological processes, such as cardiovascular diseases, metabolic diseases, autoimmune diseases, infectious diseases, and respiratory diseases. Asthma is the most common respiratory disease, which is characterized by airway inflammation and airway remodeling. Accumulating evidence has indicated that sirtuins are involved in the pathogenesis of asthma. Furthermore, some studies have suggested that sirtuin modulators are potential agents for the treatment of asthma via alteration of the expression or activity of sirtuins. In this review, we illustrate the role of sirtuins in asthma, discuss related molecular mechanisms, and evaluate the sirtuins-targeted therapy for asthma.

Inflammatory related plasma proteins involved in acute preschool wheeze

“…Cytokines derived from T2 inflammation mediate activation of Th2 responses, as shown in our study with elevated levels of IL‐6, which promotes Th2 differentiation, 24 and SIRT2, which acts pro‐inflammatory by upregulating Th2 responses 35 . SIRT2 was still upregulated at revisit after 3 months, which could be important for the development of allergic sensitization and asthma 36 . FGF21 has been shown to correlate with the frequency of circulating mast cells in asthmatic patients 37,38 and is involved in energy homoeostasis 37 .…”

“… 35 SIRT2 was still upregulated at revisit after 3 months, which could be important for the development of allergic sensitization and asthma. 36 FGF21 has been shown to correlate with the frequency of circulating mast cells in asthmatic patients 37 , 38 and is involved in energy homoeostasis. 37 Furthermore, FGF21 is a marker that can distinguish controlled from poorly controlled asthma, 39 which is in line with our findings in PW‐R being in remission.…”

Unveiling the Nexus of CD38 Overactivation, NAD+ Depletion, and Mitochondrial Dysfunction in Immunological Failure Among Virologically Suppressed HIV Patients

“…The specific complex functions of Sirtuins are beyond the scope of this article and can be found elsewhere. [9][10][11][12][13][14][15][16][17][18] Please note that the enzymatic activity of CD38(+) consume large quantities of NAD+ and generates "second messengers" like ADPR, NAADP, and cADPR. NAD(+) is also a co-factor of Sirtuins which are extremely important molecules for cell homeostasis, mitochondrial respiration (with decrease in the generation of mitochondrial ROS), and DNA repair.…”

“…These individuals, known as "Immunological non-responders" (INR), present a clinical enigma as the etiology behind this phenomenon remains largely undefined. [13][14][15][16][17][18][19] Unraveling the pathogenesis of immunological failure is crucial, given that INRs suffer from higher morbidity and mortality rates compared to full responders 20 Remarkably, several clinical interventions have been unsuccessful in reversing or improving this CD4 cell response deficit. INRs is generally defined as CD4 + T cell count below 350 cells/μl at 2 years after ART initiation, with undetectable plasma HIV RNA.…”

Aging-Related Mechanisms Contribute to Corticosteroid Insensitivity in Elderly Asthma

“…Increased CD38 activity and NAD + metabolism reduces SIRT1 deactylase activity ( Figure 2 ). In the context of asthma, SIRT1 is thought to play an anti-inflammatory role by regulating Th2 cell differentiation and inhibiting pro-inflammatory pathways such as NFκB [ 78 ]. Additionally, SIRT1 expression levels and activity have been found to be decreased in asthma and COPD patients [ 79 , 80 ].…”