Abstract
Spinal cord injury (SCI) is one of the most incapacitating neurological disorders. It involves complex pathological processes that include a primary injury and a secondary injury phase, or a delayed stage, which follows the primary injury and contributes to the aggravation of the SCI pathology. Oxidative stress, a key pathophysiological event after SCI, contributes to a cascade of inflammation, excitotoxicity, neuronal and glial apoptosis, and other processes during the secondary injury phase. In recent years, increasing evidence has demonstrated that sirtuins are protective toward the pathological process of SCI through a variety of antioxidant mechanisms. Notably, strategies that modulate the expression of sirtuins exert beneficial effects in cellular and animal models of SCI. Given the significance and novelty of sirtuins, we summarize the oxidative stress processes that occur in SCI and discuss the antioxidant effects of sirtuins in SCI. We also highlight the potential of targeting sirtuins for the treatment of SCI.
Highlights
Spinal cord injury (SCI) is a common central nervous system injury characterized by varying degrees of sensorimotor dysfunction, which can often lead to paraplegia, quadriplegia, and other pathologies that significantly affect the quality of life of a patient
It can be suggested that SIRT3 can alleviate ROSinduced oxidative stress by directly or indirectly increasing the activities of reactive oxygen species (ROS)-scavenging enzymes such as manganese superoxide dismutase (SOD) (MnSOD) and CAT and by increasing the intracellular levels of reduced glutathione. All these results suggest that SIRT3, through its deacetylation activity, may regulate a variety of enzymes, transcription factors, and biological factors that play an important role in the regulation of oxidative stress processes
Zhao et al [131] found that resveratrol could inhibit neuronal apoptosis in SCI rats, reduce tissue damage, and promote recovery of motor function by activating autophagy mediated by the SIRT1/AMP-activated protein kinase (AMPK) signaling pathway
Summary
Spinal cord injury (SCI) is a common central nervous system injury characterized by varying degrees of sensorimotor dysfunction, which can often lead to paraplegia, quadriplegia, and other pathologies that significantly affect the quality of life of a patient. The redox signaling pathways regulated by sirtuins often are the ones that, when altered, play important roles in the occurrence and development of various pathologies [28,29,30], including SCI. This suggests that sirtuins are promising antioxidant enzymes that could be molecular targets for the treatment of SCI. We provide a synopsis of the involvement of oxidative stress in SCI and summarize the results from available literature, discussing the mechanisms and therapeutic approaches that target sirtuins to protect the spinal cord from oxidative stress-induced injury after SCI
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