Abstract
Traumatic brain injury (TBI), a leading cause of morbidity worldwide, induces mechanical, persistent structural, and metabolic abnormalities in neurons and other brain-resident cells. The key pathological features of TBI include neuroinflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. These pathological processes persist for a period of time after TBIs. Sirtuins are evolutionarily conserved nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylases and mono-ADP-ribosyl transferases. The mammalian sirtuin family has seven members, referred to as Sirtuin (SIRT) 1–7. Accumulating evidence suggests that SIRT1 and SIRT3 play a neuroprotective role in TBI. Although the evidence is scant, considering the involvement of SIRT2, 4–7 in other brain injury models, they may also intervene in similar pathophysiology in TBI. Neurodegenerative diseases are generally accepted sequelae of TBI. It was found that TBI and neurodegenerative diseases have many similarities and overlaps in pathological features. Besides, sirtuins play some unique roles in some neurodegenerative diseases. Therefore, we propose that sirtuins might be a promising therapeutic target for both TBI and associated neurodegenerative diseases. In this paper, we review the neuroprotective effects of sirtuins on TBI as well as related neurodegeneration and discuss the therapeutic potential of sirtuin modulators.
Highlights
Traumatic brain injury (TBI) is a leading cause of morbidity worldwide
TBI is widely recognized as a risk factor for neurodegenerative diseases (Goldstein et al, 2012; Gardner and Yaffe, 2015; Daglas and Adlard, 2018; Gardner et al, 2018), which are characterized by a slow progressive loss of neurons or myelin sheaths and increasing disability and include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, and multiple sclerosis
It has previously been observed that pathological processes, including oxidative stress, neuroinflammation, excitotoxicity, proteinopathies, and mitochondrial dysfunction, may persist for months or years post-TBI, and these pathophysiological substrates serve as triggers yielding the progression of neurodegenerative diseases (Gentleman et al, 2004; Johnson et al, 2013a; Loane et al, 2014; Zhou et al, 2020a)
Summary
Traumatic brain injury (TBI) is a leading cause of morbidity worldwide. It is associated with long-term disability and significant healthcare expenditures and has become a priority for public health policy (Quaglio et al, 2017). Sirtuins are of vital interest in oxidative stress, neuroinflammation, blood–brain barrier (BBB) permeability, astrocyte activation, and neural apoptosis in brain injuries. The common causes of neurodegenerative diseases are neuroinflammation, excitotoxicity, oxidative stress, mitochondrial dysfunction, and proteinopathies, all of which are involved in the pathophysiology of TBI (Zhou et al, 2020a).
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