Sirtuins: Potential Therapeutic Targets for Defense against Oxidative Stress in Spinal Cord Injury

Table 1

Basic characteristics of sirtuins and the potential mechanisms in SCI.

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]

Abbreviations: SIRT: sirtuin; SCI: spinal cord injury; AMPK: AMP-activated protein kinase; phosphatase and tensin homolog: PTEN; PKCε: protein kinase C epsilon; PGC-1α: peroxisome proliferator-activated receptor-γ coactivator-1α.