Abstract
Sirtuins are evolutionarily conserved proteins that use nicotinamide adenine dinucleotide (NAD+) as a co-substrate in their enzymatic reactions. There are seven proteins (SIRT1-7) in the human sirtuin family, among which SIRT1 is the most conserved and characterized. SIRT1 in the brain, in particular, within the hypothalamus, plays crucial roles in regulating systemic energy homeostasis and circadian rhythm. Apart from this, SIRT1 has also been found to mediate beneficial effects in neurological diseases. In this review, we will first summarize how SIRT1 in the brain relates to obesity, type 2 diabetes, and circadian synchronization, and then we discuss the neuroprotective roles of brain SIRT1 in the context of cerebral ischemia and neurodegenerative disorders.
Highlights
Sirtuins are homologs of yeast silent information regulator 2 (Sir2)
This study showed that the binding of SIRT1 to the CLOCK-BMAL1 complex is rhythmic and promotes the deacetylation and degradation of the PER2 protein [19]
It is clear that SIRT1 signaling can result in the activation of PGC-1α which is protective against oxidative stress and Parkinson’s disease (PD) pathology
Summary
Sirtuins are homologs of yeast silent information regulator 2 (Sir2). Sir2 has attracted the attention of researchers given its involvement in longevity [1]. Studies have shown that SIRT1 interacts with PGC-1α to induce its transcriptional activity via deacetylation [16, 30,31,32]. SIRT1 can suppress Uncoupling protein 2 (UCP-2) in the inner mitochondrial membrane to increase levels of ATP, which is important for energy metabolism. When SIRT1 is overexpressed in the hypothalamus, either in POMC or AgRP neurons, non-obese mice exhibited increased sensitivity to leptin, as demonstrated by increased phosphorylation of STAT3 as well as reduced food intake [53].
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