Biochemical Functions and Clinical Characterizations of the Sirtuins in Diabetes-Induced Retinal Pathologies

Abstract

Diabetic retinopathy (DR) is undoubtedly one of the most prominent causes of blindness worldwide. This pathology is the most frequent microvascular complication arising from diabetes, and its incidence is increasing at a constant pace. To date, the insurgence of DR is thought to be the consequence of the intricate complex of relations connecting inflammation, the generation of free oxygen species, and the consequent oxidative stress determined by protracted hyperglycemia. The sirtuin (SIRT) family comprises 7 histone and non-histone protein deacetylases and mono (ADP-ribosyl) transferases regulating different processes, including metabolism, senescence, DNA maintenance, and cell cycle regulation. These enzymes are involved in the development of various diseases such as neurodegeneration, cardiovascular pathologies, metabolic disorders, and cancer. SIRT1, 3, 5, and 6 are key enzymes in DR since they modulate glucose metabolism, insulin sensitivity, and inflammation. Currently, indirect and direct activators of SIRTs (such as antagomir, glycyrrhizin, and resveratrol) are being developed to modulate the inflammation response arising during DR. In this review, we aim to illustrate the most important inflammatory and metabolic pathways connecting SIRT activity to DR, and to describe the most relevant SIRT activators that might be proposed as new therapeutics to treat DR.

Roles of sirtuins in asthma

“…1 ) [ 4 ]. Despite the initial recognition that SIRTs primarily play a role in deacetylation, which requires NAD + as a cofactor, a growing body of experiments have demonstrated that SIRTs can also act on many histone and non-histone targets through multiple deacylase and mono-ADP-ribosyltransferase activities, thereby participating in multiple pathophysiological processes, such as cardiovascular diseases, metabolic diseases, autoimmune diseases, infectious diseases, and respiratory diseases [ 4 , 5 , 22 – 28 ]. Notably, each SIRT has specific substrates and exerts distinct effects in respiratory diseases.…”

The Role of Sirtuins in Osteogenic Differentiation of Vascular Smooth Muscle Cells and Vascular Calcification

“…Specially, SIRT2 can protect vascular endothelial cells by inhibiting oxidative stress and regulating apoptosis ( 86 ). SIRT4 and SIRT5 are two other mitochondrial sirtuins, which have been reported to be regulators of cellular metabolism ( 87 ). For instance, mitochondrial SIRT3, 4 and 5 may affect cell metabolism and ROS homeostasis, ultimately regulating cardiovascular health ( 88 ).…”

Current Treatments and Innovations in Diabetic Retinopathy and Diabetic Macular Edema

“…Other prospects are the regulators of sirtuins (SIRTs), an enzyme family that comprises seven isoforms whose main action is the modulation of DNA repair, cell cycle, metabolism, and aging. SIRT 1,3,5, and 6 are regulators of DR; they control sensitivity to insulin, glycolysis, gluconeogenesis, and the initiation of the inflammatory process [ 94 , 95 ]. A glycoside extracted from the roots of the licorice plant, glycyrrhizin, when administered to diabetic animal models was able to reduce ROS, IL-1β, TNF-α, cleaved caspase 3 levels, along with retinal vasculature permeability [ 95 ].…”