|
Class | Sirtuins | Intracellular distribution | Activity | Function | Potential mechanisms |
|
I | SIRT1 | Nucleus, cytoplasm | Deacetylase | Oxidative stress, inflammation, apoptosis, autophagy, metabolism | SIRT1 activated by resveratrol inhibits neuronal apoptosis in SCI rats, reduces tissue damage, and promotes motor function recovery by activating autophagy mediated by the SIRT1/AMPK signaling pathway [131]
SIRT1 activated by resveratrol promotes sonic hedgehog signaling to exert antioxidant and anti-inflammatory effects to inhibit fibrous scar formation after SCI [135]
MLN4924 significantly attenuates oxidative stress and neuronal cell death by regulating SIRT1 expression during spinal cord ischemia-reperfusion injury [30]
miR-448 inhibits neuronal apoptosis and improves neurological function by upregulating SIRT1, thereby alleviating spinal cord ischemia-reperfusion injury [142]
SIRT1 exerts neuroprotective effects by downregulating Wnt/β-catenin signaling to inhibit microglia activation, thereby reducing inflammation and cellular stress in the early stages of SCI [144]
The SIRT1/Nrf2 pathway in astrocytes can be activated by NFAT5, which exerts antioxidative stress effects against oxygen-glucose-serum deprivation/restoration damage [145]. |
| SIRT2 | Nucleus, cytoplasm | Deacetylase | Cell cycle, oxidative stress, inflammation | SIRT2 promotes the differentiation of ependymal stem cell into neurons after SCI by increasing the deacetylation of stable Ac-α-tubulin in microtubules to improve neural recovery [147] |
| SIRT3 | Mitochondria | Deacetylase | Oxidative stress, apoptosis, autophagy, metabolism | SIRT3 and PGC-1α protect rat spinal cord motor neurons from mutant SOD1(G93A)-induced mitochondrial fragmentation and neuronal cell death by maintaining mitochondrial dynamics [148] |
II | SIRT4 | Mitochondria | Deacetylase, ADP-ribosyl transferase | Inflammation, oxidative stress, metabolism | SIRT4 inhibits the antineuroinflammatory activity of regulatory T cells infiltrating in the traumatically injured spinal cord by suppressing the AMPK signaling pathway [149] |
III | SIRT5 | Mitochondria | Deacetylase, desuccinylase, demalonylase | Oxidative stress, apoptosis, metabolism | SIRT5 plays a major role in PKCε-mediated neuroprotection against cortical degeneration and neural cell death following cerebral ischemia [150] |
IV | SIRT6 | Nucleus | Deacetylase, demyristoylase, depalmitoylase, ADP-ribosyl transferase | DNA repair, oxidative stress, apoptosis, autophagy, inflammation, metabolism | SIRT6 could act as a protective factor to attenuate SCI by inhibiting inflammation, oxidative stress, and cell apoptosis [152] |
| SIRT7 | Nucleolus | Deacetylase | Oxidative stress, apoptosis, rRNA transcription | SIRT7 may protect neurons from oxygen-glucose deprivation and reoxygenation-induced damage by regulating the p53-mediated proapoptotic signaling pathway [154] |
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