Progress of deacetylase SIRTs in pathogenesis of Parkinson's disease

doi:10.16352/j.issn.1001-6325.2024.11.1603

Abstract

Abstract: Sirtuins(SIRTs), a group of NAD⁺ dependent deacetylases, have attracted considerable attention in the field of neuro-degenerative diseases, especially Parkinson's disease (PD). They have critical impacts on cell survival and death through modulation of various biological processes, such as intracellular metabolism, stress response and DNA repair. In the pathogenesis of PD, Sirtuins play a crucial role and associated with pathophysiological processes such as mitochondrial function, oxidative stress, and neuronal apoptosis. Activation of Sirtuins alleviates dyskinesia and neuronal damage in animal models of PD and also regulates the aggregation and clearance of α-synuclein, a pathological feature of the disease. Therefore, the modulation of Sirtuins is a potential strategy for treating PD.

Key words: Parkinson's disease, deacetylase Sirtuins, α-synuclein

CLC Number:

FANG Xue, SHI Jin, LI Haining, YANG Juan. Progress of deacetylase SIRTs in pathogenesis of Parkinson's disease[J]. Basic & Clinical Medicine, 2024, 44(11): 1603-1607.

References

[1] Chojdak-Lukasiewicz J, Bizon A, Waliszewska-Prosol M, et al. Role of Sirtuins in physiology and diseases of the central nervous system[J]. Biomedicines, 2022, 10.doi:10.3390/biomedicines10102434.
[2] Yeong KY, Berdigaliyev N, Chang Y. Sirtuins and their implications in neurodegenerative diseases from a drug discovery perspective[J]. ACS Chem Neurosci, 2020, 11:4073-91.doi:10.1021/acschemneuro.0c00696.
[3] Khan H, Tiwari P, Kaur A, et al. Sirtuin acetylation and deacetylation: a complex paradigm in neurodegenerative disease[J]. Mol Neurobiol, 2021, 58:3903-17.doi:10.1007/s12035-021-02387-w.
[4] Lei Y, Wang J, Wang D, et al. SIRT1 in forebrain excitatory neurons produces sexually dimorphic effects on depression-related behaviors and modulates neuronal excitability and synaptic transmission in the medial prefrontal cortex[J]. Mol Psychiatry, 2020, 25:1094-111.doi:10.1038/s41380-019-0352-1.
[5] Singh V, Ubaid S. Role of silent information regulator 1 (SIRT1) in regulating oxidative stress and inflammation[J]. Inflammation, 2020, 43:1589-1598.doi:10.1007/s10753-020-01242-9.
[6] Huang Q, Su H, Qi B, et al. A SIRT1 activator, ginsenoside Rc, promotes energy metabolism in cardiomyocytes and neurons[J]. J Am Chem Soc, 2021, 143:1416-1427.doi:10.1021/jacs.0c10836.
[7] Li X, Feng Y, Wang XX, et al. The critical role of SIRT1 in Parkinson's disease: mechanism and therapeutic considerations[J]. Aging Dis, 2020, 11:1608-1622.doi:10.14336/AD.2020.0216.
[8] Jiao F, Gong Z. The beneficial roles of SIRT1 in neuroinflammation-related diseases[J]. Oxid Med Cell Longev, 2020, 2020:6782872.doi:10.1155/2020/6782872.
[9] Haque ME, Akther M, Azam S, et al. Targeting alpha-synuclein aggregation and its role in mitochondrial dysfunction in Parkinson's disease[J]. Br J Pharmacol, 2022, 179:23-45.doi:10.1111/bph.15684.
[10] Dong Z, Wang Y, Hao C, et al. Sanghuangporus sanghuang extract extended the lifespan and healthspan of caenorhabditis elegans via DAF-16/SIR-2.1[J]. Front Pharmacol, 2023, 14:1136897.doi:10.3389/fphar.2023.1136897.
[11] Kaitsuka T, Matsushita M, Matsushita N. Regulation of hypoxic signaling and oxidative stress via the microRNA-SIRT2 axis and its relationship with aging-related diseases[J]. Cells, 2021, 10.doi:10.3390/cells10123316.
[12] Yang Q, Zhou Y, Sun Y, et al. Will Sirtuins be promising therapeutic targets for TBI and associated neurodegenerative diseases?[J]. Front Neurosci, 2020, 14:791.doi:10.3389/fnins.2020.00791.
[13] Saramowicz K, Siwecka N, Galita G, et al. Alpha-synuclein contribution to neuronal and Glial damage in Parkinson's disease[J]. Int J Mol Sci, 2023, 25.doi:10.3390/ijms25010360.
[14] Akbulut KG, Keskin-Aktan A, Abgarmi SA, et al. The role of SIRT2 inhibition on the aging process of brain in male rats[J]. Aging Brain, 2023, 4:100087.doi:10.1016/j.nbas.2023.100087.
[15] He L, Wang J, Yang Y, et al. Mitochondrial Sirtuins in Parkinson's Disease[J]. Neurochem Res, 2022, 47:1491-1502.doi:10.1007/s11064-022-03560-w.
[16] He M, Chiang HH, Luo H, et al. An acetylation switch of the NLRP3 inflammasome regulates aging-associated chronic inflammation and insulin resistance[J]. Cell Metab, 2020, 31:580-91 e5.doi:10.1016/j.cmet.2020.01.009.
[17] Nie H, Hong Y, Lu X, et al. SIRT2 mediates oxidative stress-induced apoptosis of differentiated PC12 cells[J]. Neuroreport, 2014, 25:838-842.doi:10.1097/WNR.0000000000000192.
[18] Garmendia-Berges M, Sola-Sevilla N, Mera-Delgado M, et al. Age-associated changes of Sirtuin 2 expression in CNS and the periphery[J]. Biology (Basel), 2023, 12.doi:10.3390/biology12121476.
[19] Hu J, Kan T, Hu X. Sirt3 regulates mitophagy level to promote diabetic corneal epithelial wound healing[J]. Exp Eye Res, 2019, 181:223-231.doi:10.1016/j.exer.2019.02.011.
[20] Zhou TY, Wu YG, Zhang YZ, et al. SIRT3 retards intervertebral disc degeneration by anti-oxidative stress by activating the SIRT3/FOXO3/SOD2 signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23:9180-9188.doi:10.26355/eurrev_201911_19408.
[21] Shefa U, Jeong NY, Song IO, et al. Mitophagy links oxidative stress conditions and neurodegenerative diseases[J]. Neural Regen Res, 2019, 14:749-756.doi:10.4103/1673-5374.249218.
[22] Zhang S, Ma Y, Feng J. Neuroprotective mechanisms of epsilon-viniferin in a rotenone-induced cell model of Parkinson's disease: significance of SIRT3-mediated FOXO3 deacetylation[J]. Neural Regen Res, 2020, 15:2143-2153.doi:10.4103/1673-5374.282264.
[23] Wang R, Sun H, Wang G, et al. Imbalance of lysine acetylation contributes to the pathogenesis of Parkinson's disease[J]. Int J Mol Sci, 2020, 21.doi:10.3390/ijms21197182.
[24] Luo H, Peng C, Xu X, et al. The protective effects of mogroside V against neuronal damages by attenuating mitochondrial dysfunction via upregulating Sirtuin3[J]. Mol Neurobiol, 2022, 59:2068-2084.doi:10.1007/s12035-021-02689-z.
[25] Zeng R, Wang X, Zhou Q, et al. Icariin protects rotenone-induced neurotoxicity through induction of SIRT3[J]. Toxicol Appl Pharmacol, 2019, 379:114639.doi:10.1016/j.taap.2019.114639.