TABLE 1.
Function of sirtuins in brain injury.
| Sirtuins | Roles | Pathway/Mechanism | Models | Activation/Overexpression | Inhibition/Silence |
| SIRT1 | Protective | Astrocyte activation | TBI | ↓ (Li et al., 2017) | – |
| Protective | BBB integrality | SAH and aging | ↑ (Qian et al., 2017; Zhao et al., 2017; Stamatovic et al., 2019) | ↓ (Zhou et al., 2014; Zhao et al., 2017; Stamatovic et al., 2019) | |
| Protective | Inflammation | TBI | ↓ (Zou et al., 2018) | – | |
| Protective | Microglia activation and polarization | TBI | ↓ (Chen et al., 2017, Chen et al., 2018a) | – | |
| Protective | Oxidative stress | TBI | ↓ (Zou et al., 2018) | – | |
| Protective | Excitotoxic lesion | Cortical neurons | ↓ (Jia et al., 2016; Marin et al., 2019) | – | |
| Protective | Vascular repair | Ischemic brain tissues | ↑ (Choi et al., 2017) | – | |
| Protective | Endothelial cell apoptosis | SAH | – | ↑ (Zhou et al., 2014) | |
| Protective | Apoptosis of neurons | TBI | ↑ (Zhao et al., 2012) | ↓ (Zhao et al., 2012) | |
| Protective | Axon genesis and axon elongation | Embryonic hippocampal neurons | ↑ (Li et al., 2013) | – | |
| Protective | Mitochondrial damage | TBI | ↓ (Yang et al., 2017) | ↑ (Yang et al., 2017) | |
| Protective | Tau hyperphosphorylation | Rat model of brain insulin resistance | ↓ (Du et al., 2014) | ||
| SIRT2 | Protective | BBB integrality | TBI | – | ↓ (Yuan et al., 2016) |
| Protective | Microglia and inflammation | LPS induced neuroinflammation models | ↓ (Pais et al., 2013) | – | |
| SIRT3 | Detrimental | Ceramide accumulation | Stoke | ↑ (Novgorodov et al., 2016) | – |
| Protective | Oxidative stress | TBI; SAH; I/R; OGD | ↓ (Rangarajan et al., 2015; Shi et al., 2017; Zhao et al., 2018; Tu et al., 2019) | ↑ (Rangarajan et al., 2015; Huang et al., 2016; Shi et al., 2017; Tu et al., 2019) | |
| Protective | Autophagy of neurons | OGD | ↑ (Dai et al., 2017) | – | |
| Protective | Excitotoxicity | Cortical neurons | ↓ (Kim et al., 2011) | – | |
| Protective | Amyloid β peptide | Chinese Hamster Ovarian (CHO) cells | ↓ (Ramesh et al., 2018) | – | |
| SIRT4 | Protective | Glutamate transport function | Sirt4 KO mice | – | ↓ (Shih et al., 2014) |
| Protective | Excitotoxicity | Cortical neurons | ↓ (Marin et al., 2019) | – | |
| SIRT5 | Detrimental | BBB permeability | I/R | – | ↓ (Diaz-Cañestro et al., 2018) |
| SIRT6 | Protective | Oxidative stress | Stroke; I/R; OGD | ↓ (Zhang W. et al., 2017; Liberale et al., 2019) | ↑ (Liberale et al., 2019) |
| Protective | BBB integrality | Stoke | ↑ (Liberale et al., 2019) | ↓ (Liberale et al., 2019) | |
| SIRT7 | Protective | Oxidative stress | I/R | ↓ (Lv et al., 2017) | – |
| Protective | Apoptosis | I/R | ↓ (Lv et al., 2017) | – |