Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Abstract

Neuroinflammatory disorder is a general term that is associated with the progressive loss of neuronal structure or function. At present, the widely studied diseases with neuroinflammatory components are mainly divided into neurodegenerative and neuropsychiatric diseases, namely, Alzheimer’s disease, Parkinson’s disease, depression, stroke, and so on. An appropriate neuroinflammatory response can promote brain homeostasis, while excessive neuroinflammation can inhibit neuronal regeneration and damage the central nervous system. Apart from the symptomatic treatment with cholinesterase inhibitors, antidepressants/anxiolytics, and neuroprotective drugs, the treatment of neuroinflammation is a promising therapeutic method. Sirtuins are a host of class III histone deacetylases, that require nicotinamide adenine dinucleotide for their lysine residue deacetylase activity. The role of sirtuin 2 (SIRT2), one of the sirtuins, in modulating senescence, myelin formation, autophagy, and inflammation has been widely studied. SIRT2 is associated with many neuroinflammatory disorders considering it has deacetylation properties, that regulate the entire immune homeostasis. The aim of this review was to summarize the latest progress in regulating the effects of SIRT2 on immune homeostasis in neuroinflammatory disorders. The overall structure and catalytic properties of SIRT2, the selective inhibitors of SIRT2, the relationship between immune homeostasis and SIRT2, and the multitasking role of SIRT2 in several diseases with neuroinflammatory components were discussed.

Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain

“…AXIN1, for example, a regulator molecule of the Wnt signaling pathways [ 75 ], has been shown to correlate with disease severity in endometriosis [ 76 ]. SIRT2 has a wide range of regulatory functions ranging from neuronal to immunological and metabolic homeostasis [ 77 , 78 ]. Our study, together with other protein disease signature (PDS) studies, shows the importance of analyzing multiple inflammatory markers and comorbidities to explore a more complete picture of a disease.…”

Oligodendrocyte‐derived exosomes‐containing SIRT2 ameliorates depressive‐like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK‐3β pathway in depressed mice

“… 22 The transcellular delivery of this protein from oligodendrocytes to neurons via exosomes plays a vital role in CNS function. 16 SIRT2 is implicated in neuropsychiatric disorders, 23 and clinical studies have indicated that SIRT2 transcript is reduced in peripheral leukocytes and hippocampal tissues of depressed patients. 24 , 25 In rodents, reduced hippocampal SIRT2 is associated with the progression of depression and impaired neuroplasticity, while SIRT2 overexpression can enhance hippocampal neurogenesis and alleviate depressive symptoms.…”

Inhibiting SIRT-2 by AK-7 restrains airway inflammation and oxidative damage promoting lung resurgence through NF-kB and MAP kinase signaling pathway

“…SIRT-2 has been extensively examined for its involvement in influencing senescence, myelin formation, autophagy, and inflammation. These has been linked with numerous neuroinflammatory pathologies as it contains deacetylation characteristics that affect immune homeostasis ( 27 ). SIRT-3, SIRT-4, and SIRT-5 are mitochondrial proteins that are strongly connected to mitochondrial function and play a key role in the development of COPD-associated mitochondrial dysfunction.…”