Sirtuins: Promising Therapeutic Targets to Treat Ischemic Stroke

Abstract

Stroke is a major cause of mortality and disability globally, with ischemic stroke (IS) accounting for over 80% of all stroke cases. The pathological process of IS involves numerous signal molecules, among which are the highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes known as sirtuins (SIRTs). SIRTs modulate various biological processes, including cell differentiation, energy metabolism, DNA repair, inflammation, and oxidative stress. Importantly, several studies have reported a correlation between SIRTs and IS. This review introduces the general aspects of SIRTs, including their distribution, subcellular location, enzyme activity, and substrate. We also discuss their regulatory roles and potential mechanisms in IS. Finally, we describe the current therapeutic methods based on SIRTs, such as pharmacotherapy, non-pharmacological therapeutic/rehabilitative interventions, epigenetic regulators, potential molecules, and stem cell-derived exosome therapy. The data collected in this study will potentially contribute to both clinical and fundamental research on SIRTs, geared towards developing effective therapeutic candidates for future treatment of IS.

Keywords

• sirtuins
• ischemic stroke
• deacetylation
• neuroprotection