Role and Possible Mechanisms of Sirt1 in Depression

Abstract

Depression is a common, devastating illness. Due to complicated causes and limited treatments, depression is still a major problem that plagues the world. Silent information regulator 1 (Sirt1) is a deacetylase at the consumption of NAD+ and is involved in gene silencing, cell cycle, fat and glucose metabolism, cellular oxidative stress, and senescence. Sirt1 has now become a critical therapeutic target for a number of diseases. Recently, a genetic study has received considerable attention for depression and found that Sirt1 is a potential gene target. In this short review article, we attempt to present an up-to-date knowledge of depression and Sirt1 of the sirtuin family, describe the different effects of Sirt1 on depression, and further discuss possible mechanisms of Sirt1 including glial activation, neurogenesis, circadian control, and potential signaling molecules. Thus, it will open a new avenue for clinical treatment of depression.

SIRT1 accelerates the progression of activity-based anorexia

“…The consequences of SIRT1 activation that we describe here, and those established by others [7][8][9]11,12,14,16,48,67,68 , overlap closely with physiological changes associated with AN pathologies, which supports our hypothesis of AN development (Fig. 4g).…”

Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway

“…It is widely expressed in the CNS and involved in the maintenance of physiological brain functions and exhibits neuroprotective and anti-inflammatory effects in many neurodegenerative diseases. Several studies have shown that SIRT1 deregulation contributes to the pathogenesis of MDD (39, 40). Recent large-scale GWAS studies showed that a SNP close to SIRT1 loci is associated with MDD in Chinese women (41).…”

Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation

“…Recent studies suggest that the beneficial effect of antidepressant drugs is mediated via stimulation of adult hippocampal neurogenesis and subsequent increase in hippocampal plasticity. Changes in hippocampal neurons can play an important role in the pathogenesis of depression, involving the possible mechanism of ERK (extracellular signal-regulated kinase) pathway [7], AMPK (Adenosine monophosphate-activated protein kinase) pathway [8], GABAergic dysfunction in the nucleus accumbens (NAc) [9], epigenetic events altering the chromatin structure and thus modulating expression of genes [10], Sirt1 (silent information regulator 1) at the consumption of NAD+ [11], BDNF pathway [12,13], etc. However, mitochondrial energy metabolism in depression remains poorly understood although the action of the above mentioned signalings, at least in part, relies on energy metabolism.…”