Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System
Abstract
:1. Introduction
2. Molecular Structure and Function of Sirt3
2.1. Sirtuin Family and Sirt3
2.2. Molecular Function of Sirt3
3. Cellular Function of Sirt3 in the CNS
3.1. Sirt3 and Neurons
3.2. Sirt3 and Astrocytes
3.3. Sirt3 and Microglia
4. Sirt3 and Neurodegenerative Diseases
4.1. Sirt3 and Alzheimer’s Disease
4.2. Sirt3 and Parkinson’s Disease
4.3. Sirt3 and Huntington’s Disease
4.4. Sirt3 and Amyotrophic Lateral Sclerosis
4.5. Sirt3 and Multiple Sclerosis
5. Conclusions and Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Neurodegenerative Disease | Mechanism | Experimental Setting | Research |
---|---|---|---|
AD | ROS in mitochondria increase Sirt3 expression. | Cell model | [73] |
Pharmacological enhancement of mitochondrial ROS increases the expression of Sirt3 in primary hippocampal cultures. | AD mouse model and cell model | [74] | |
PACAP stimulates the production of mitochondrial Sirt3 and reduces neuronal death. | Postmortem human tissue, triple transgenic mouse model, and cell model | [75] | |
Amyloid-β increases levels of total tau and acetylated tau through its modulation of Sirt3. | Postmortem human tissue | [76] | |
APOE4 reduces ATP production by modulating the PGC-1α-Sirt3 signaling pathway, triggering mitochondrial oxidative stress and disrupting synaptic function. | Postmortem human tissue | [77] | |
Sirt3 may mediate the neuroprotection of ketones by increasing neuronal energy metabolism. | APOE4 mouse model | [78] | |
Alleviation of Aβ 42-induced neuronal metabolic dysfunction occurs via the THRB/Sirt3 axis and improves cognition. | APPTG mouse model | [79] | |
Activation of mitophagy and mitochondrial unfolded protein response occurs. | APP/PS1 mouse model | [80] | |
PD | IC87201 and ZL006 reduce ROS production and improve mitochondrial dysfunction by increasing the expression of Sirt3 after MPP+ exposure. | MPP+-induced primary cortical neuron cell models | [81] |
Sirt3 has a possible role in MPTP-induced neurodegeneration by preserving the free radical scavenging capacity of mitochondria. | Sirt3 null mouse model | [82] | |
Sirt3 overexpression dramatically increases cell viability, decreases cell apoptosis, prevents the accumulation of α-synuclein, suppresses the reduction of SOD and glutathione, decreases ROS generation, and alleviates MMP collapse induced by rotenone. | PD cell model | [83] | |
Sirt3 rescues neurons through the stabilization of mitochondrial biogenetics. | Virally expressed mutant α-synuclein rat model of parkinsonism | [84] | |
Curcumin lowers ROS levels in SH-SY5Y cells and upregulates Sirt3 expression. | SH-SY5Y cell models | [85] | |
miR-494-3p downregulation increases Sirt3 expression, reduces oxidative stress, and improves dyskinesia. | MPTP-induced PD mouse model and SH-SY5Y cell model | [86] | |
Saikosaponin-d exerts a neuroprotective effect by upregulating Sirt3 expression and alleviating oxidative stress damage. | MPP+-induced SH-SY5Y cell models | [87] | |
Sirt3 mediates SOD2 deacetylation to reduce ROS accumulation and to restore mitochondrial function, thereby preventing apoptosis. | 6-OHDA-treated rat, MPTP-treated mouse, and zebrafish models | [88] | |
Regulation of Sirt3 in mitochondrial functions and oxidative stress occurs in PD. | Sirt3 null mouse and PD mouse models | [89] | |
Upregulated Sirt3 mitigates the protective effect of mitochondrial dysfunction on neuronal damage. | SH-SY5Y cell models | [90] | |
HD | Knockdown of Sirt3 significantly inhibits viniferin-mediated AMP-activated kinase activation and diminishes the neuroprotective effects of viniferin. | Mutant HTT cell model | [91] |
Increased Sirt3 levels and/or activity reduce oxidative damage. | Cell model, HD knockin mouse model, and Huntington’s disease transgenic (YAC128) mouse model | [92,93,94] | |
Sirt3 protects neurons against metabolic and oxidative stress by reducing mitochondrial superoxide levels, stabilizing cellular and mitochondrial Ca2+ homeostasis, and inhibiting mitochondrial membrane permeability transition pore formation to prevent apoptosis. | Cell model and HD mouse model | [95] | |
Sirt3 overexpression promotes the antioxidant effect of cells expressing mutant HTT, leading to enhanced mitochondrial function and balanced dynamics. | Postmortem human tissue and primary striatal neuron cell model | [96] | |
ALS | Sirt3 protects against mitochondrial fragmentation and neuronal cell death with mutant SOD1 (G93A). | SOD1G93A transgenic mouse model and primary cortical neuronal cell model | [97] |
Overexpression of Sirt3 increases NADPH levels and protects from oxidative-stress-induced cell death. | Sirt3 mouse model | [98] | |
Grape wine polyphenols prevent axonal apoptosis and act via mitochondrial Sirt3 activation in axons. | Primary cortical neuronal cell model | [99] | |
Sirt3 can restore neuronal mitochondrial fragmentation and transport disorders, reducing neuronal death, and protects against mitochondrial alterations. | SOD1-mutant cell model | [100,101] | |
MS | The EA protects muscle tissue from cuprizone-induced demyelination by overexpressing Sirt3 to protect mitochondria and to reduce oxidative stress. | Mouse model | [102] |
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Zhang, H.; Dai, S.; Yang, Y.; Wei, J.; Li, X.; Luo, P.; Jiang, X. Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System. Biomolecules 2023, 13, 735. https://doi.org/10.3390/biom13050735
Zhang H, Dai S, Yang Y, Wei J, Li X, Luo P, Jiang X. Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System. Biomolecules. 2023; 13(5):735. https://doi.org/10.3390/biom13050735
Chicago/Turabian StyleZhang, Haofuzi, Shuhui Dai, Yuefan Yang, Jialiang Wei, Xin Li, Peng Luo, and Xiaofan Jiang. 2023. "Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System" Biomolecules 13, no. 5: 735. https://doi.org/10.3390/biom13050735