Abstract
Selenium (Se) and its compounds have been reported to have great potential in the prevention and treatment of Alzheimer’s disease (AD). However, little is known about the functional mechanism of Se in these processes, limiting its further clinical application. Se exerts its biological functions mainly through selenoproteins, which play vital roles in maintaining optimal brain function. Therefore, selenoproteins, especially brain function-associated selenoproteins, may be involved in the pathogenesis of AD. Here, we analyze the expression and distribution of 25 selenoproteins in the brain and summarize the relationships between selenoproteins and brain function by reviewing recent literature and information contained in relevant databases to identify selenoproteins (GPX4, SELENOP, SELENOK, SELENOT, GPX1, SELENOM, SELENOS, and SELENOW) that are highly expressed specifically in AD-related brain regions and closely associated with brain function. Finally, the potential functions of these selenoproteins in AD are discussed, for example, the function of GPX4 in ferroptosis and the effects of the endoplasmic reticulum (ER)-resident protein SELENOK on Ca2+ homeostasis and receptor-mediated synaptic functions. This review discusses selenoproteins that are closely associated with brain function and the relevant pathways of their involvement in AD pathology to provide new directions for research on the mechanism of Se in AD.
Highlights
Over the past decades, selenium (Se) and its compounds have mainly been the focus of research on regulation of development and the immune system and on antitumor properties due to their strong antioxidant activities (Rayman, 2000; Schomburg, 2016)
This map shows that the high expression levels of the brain selenoproteins selenophosphate synthetase 2 (SEPHS2), SELENOK, SELENOR, DIO2, SELENOS, SELENOF, SELENOW, and SELENOT are even more pronounced in the hippocampal and cortical regions than in other brain regions, suggesting that these selenoproteins might be strongly associated with Alzheimer’s disease (AD)
As selenoproteins are the representatives of Se performing its physiological functions, investigation of the functions of selenoproteins in the brain and the association of selenoproteins with AD pathology might be critical for elucidating the mechanism of action of Se
Summary
Selenium (Se) and its compounds have mainly been the focus of research on regulation of development and the immune system and on antitumor properties due to their strong antioxidant activities (Rayman, 2000; Schomburg, 2016). van Eersel et al (2010) and Jin et al (2017) used transgenic animal models of AD to show that sodium selenate reduced tau protein phosphorylation and ameliorated cognitive impairment in AD mice by regulating the activity of protein phosphatase 2A (PP2A) (Ishrat et al, 2009; Lovell et al, 2009; Corcoran et al, 2010; van Eersel et al, 2010; Jin et al, 2017), which undoubtedly promoted research regarding Se in AD prevention and treatment. Neuron-specific Trsp-knockout mice had significantly decreased expression levels of selenoproteins in the brain and showed delayed growth, loss of balance, and extensive neuronal degeneration (Wirth et al, 2010). GPX4-regulated ferroptosis can induce progressive cognitive impairment and hippocampal neurodegeneration in mice (Hambright et al, 2017) These brain functionrelated selenoproteins may be involved in the occurrence and development of AD. This review analyzes the expression and distribution of selenoproteins in the brain, assesses the associations between various selenoproteins and brain function and the potential of these selenoproteins in AD research, and discusses the roles of these selenoproteins in AD pathology
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