Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders

Chen, Xiuqi; Lu, Wenmei; Wu, Danhong

doi:10.3389/fnins.2021.614107

Cited by 36 publications

(39 citation statements)

References 88 publications

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“…In our proteomics analysis, in addition to identifying the myelination‐related protein regulated by caffeine in hypoxic‐ischemic WMD, it is more important to identify the protein interacting with myelination‐related protein–sirtuin 2 (SIRT2). As a nicotinamide adenine dinucleotide‐dependent deacetylase, SIRT2 is mainly expressed in myelinating glia of the central nervous system (CNS) and plays an important role in neurological diseases 55–58 . Pathological features, such as neuroinflammation, synaptic dysfunction, metabolic abnormalities, and oxidative stress, are affected by SIRT2 expression 55 .…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic‐ischemic white matter damage

Liu

Zhang

et al. 2022

CNS Neurosci Ther

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Aim White matter damage (WMD) is the main cause of cerebral palsy and cognitive impairment in premature infants. Although caffeine has been shown to possess neuroprotective effects in neonatal rats with hypoxic‐ischemic WMD, the mechanisms underlying these protective effects are unclear. Herein, proteins modulated by caffeine in neonatal rats with hypoxic‐ischemic WMD were evaluated. Methods We identified differential proteins and performed functional enrichment analyses between the Sham, hypoxic‐ischemic WMD (HI), and HI+caffeine‐treated WMD (Caffeine) groups. Confirmed the changes and effect of proteins in animal models and determined cognitive impairment via water maze experiments. Results In paraventricular tissue, 47 differential proteins were identified between the Sham, HI, and Caffeine groups. Functional enrichment analyses showed that these proteins were related to myelination and axon formation. In particular, the myelin basic protein (MBP), proteolipid protein, myelin‐associated glycoprotein precursor, and sirtiun 2 (SIRT2) levels were reduced in the hypoxic‐ischemic WMD group, and this effect could be prevented by caffeine. Caffeine alleviated the hypoxic‐ischemic WMD‐induced cognitive impairment and improved MBP, synaptophysin, and postsynaptic density protein 95 protein levels after hypoxic‐ischemic WMD by preventing the HI‐induced downregulation of SIRT2; these effects were subsequently attenuated by the SIRT2 inhibitor AK‐7. Conclusion Caffeine may have clinical applications in the management of prophylactic hypoxic‐ischemic WMD; its effects may be mediated by proteins related to myelin development and synapse formation through SIRT2.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic‐ischemic white matter damage

Liu

Zhang

et al. 2022

CNS Neurosci Ther

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“…Although SIRT2 concentrations are higher in the cytosol, during cell cycle G2/M transition they are translocated to the nucleus, where they regulate H4K20 methylation by deacetylation of histone H4K16, which is key in chromosome compaction [ 109 ]. Paradoxically, there is evidence of cell proliferation disruption and cell cycle arrest in overexpressing SIRT2 lung cancer cells [ 110 ].…”

Section: Sirtuinsmentioning

confidence: 99%

Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

Figarola-Centurión

Escoto-Delgadillo

González-Enríquez

et al. 2022

IJMS

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HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain–blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer’s and Parkinson’s disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV.

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“…SIRT2 also has important biological functions and has been found to be associated with many diseases, including cancer, neurological disorders, and cardiovascular diseases ( Chen et al, 2020a ; Chen et al, 2021b ; Taneja et al, 2021 ). SIRT2 is unique because it is the only sirtuin to be mainly distributed in the cytoplasm and can also be found in the nucleus ( Vaquero et al, 2006 ).…”

Section: The Roles Of Sirtuins In Vascular Calcificationmentioning

confidence: 99%

Mammalian Sirtuins and Their Relevance in Vascular Calcification

Pan

Ruan

et al. 2022

Front. Pharmacol.

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Cardiovascular diseases are a group of diseases with high morbidity and mortality that affect millions of people each year. Vascular calcification (VC) is an active process that involves the mineral deposition of calcium-phosphate complexes. VC is closely related to cardiovascular diseases, such as hypertension, heart failure, and calcific aortic stenosis, and is a type of ectopic calcification that occurs in the vessel walls. The sirtuins (silent mating-type information regulation 2; SIRTs), are a family of histone deacetylases whose function relies on nicotinamide adenine dinucleotide (NAD+). They have non-negligible functions in the regulation of energy metabolism, senescence, apoptosis, and other biological processes. Sirtuins have important effects on bone homeostasis and VC processes that share many similarities with bone formation. Sirtuins have been confirmed to deacetylate a variety of target proteins related to the occurrence and development of VC, thereby affecting the process of VC and providing new possibilities for the prevention and treatment of cardiovascular diseases. To facilitate the understanding of vascular calcification and accelerate the development of cardiovascular drugs, we reviewed and summarized recent research progress on the relationship between different types of sirtuins and VC.

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Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders

Cited by 36 publications

References 88 publications

Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic‐ischemic white matter damage

Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic‐ischemic white matter damage

Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

Mammalian Sirtuins and Their Relevance in Vascular Calcification

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