Role of Sirtuins in Physiology and Diseases of the Central Nervous System

Abstract

Silent information regulators, sirtuins (SIRTs), are a family of enzymes which take part in major posttranslational modifications of proteins and contribute to multiple cellular processes, including metabolic and energetic transformations, as well as regulation of the cell cycle. Recently, SIRTs have gained increased attention as the object of research because of their multidirectional activity and possible role in the complex pathomechanisms underlying human diseases. The aim of this study was to review a current literature evidence of SIRTs’ role in the physiology and pathology of the central nervous system (CNS). SIRTs have been demonstrated to be crucial players in the crosstalk between neuroinflammation, neurodegeneration, and metabolic alterations. The elucidation of SIRTs’ role in the background of various CNS diseases offers a chance to define relevant markers of their progression and promising candidates for novel therapeutic targets. Possible diagnostic and therapeutic implications from SIRTs-related investigations are discussed, as well as their future directions and associated challenges.

Nicotinamide Prevents Diabetic Brain Inflammation via NAD+-Dependent Deacetylation Mechanisms

“…As such, NAD+ replenishment is emerging as a potential therapy to combat the development of neurological manifestations in diabetic subjects [ 21 ]. Insomuch as NAD+ acts as an obligatory coenzyme for a class of cellular protein deacetylases collectively known as sirtuins [ 11 ], the mechanisms underlying the anti-inflammatory effects by NAD+-increasing approaches may involve direct effects on such enzymes; however, the impact of NAD+-mediated deacetylation on NFκB signaling in brains of diabetic mice have not been addressed in any previous study. In this context, to our knowledge, our findings are the first to show the contribution of NAD+-related deacetylation mechanisms in the attenuation of brain inflammation and microglial activation.…”

“…NAD+ depletion profoundly shapes the clinical outcome of diabetic brain inflammation [ 11 ]. As such, changes in NAD+ metabolism observed in diabetic subjects may reflect endogenous declines of NAD+ precursors (including NAM and their main related derivatives).…”

“…NAD+-dependent histone deacetylases, also known as sirtuins (SIRT), are a class of NAD+-consuming enzyme which is involved in the deacetylation of different signaling proteins [ 11 ]. Particularly, SIRT1 is able to inhibit NFκB action by specifically deacetylating the p65 subunit, thereby suppressing inflammation [ 15 ].…”

Does resveratrol improve cognition in humans? A scientometric study to an in‐depth review

“…The protein deacetylase SIRT1 is the mammalian homolog of the yeast silent information regulator-2 (SIRT2), a member of the sirtuin family that has received considerable interest as a potential mediator of lifespan extension in a number of model animals. 48 In the clinical experiment of AD patients, RES reduces Aβ levels, improves brain volume, reduces the Mini-mental status score, and improves AD scores. [49][50][51] Furthermore, it is indicated that physiological doses of RES are safe and well tolerated.…”

“…Notably, RES can also modulate different molecular pathways in neurodegenerative diseases by specifically activating silent information regulator‐1 (SIRT1). The protein deacetylase SIRT1 is the mammalian homolog of the yeast silent information regulator‐2 (SIRT2), a member of the sirtuin family that has received considerable interest as a potential mediator of lifespan extension in a number of model animals 48 …”