Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

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.

The Role of Selenium in Pathologies: An Updated Review

“…Moreover, Gpx1 may act as a neuromodulator, impacting on neurodegenerative and neuropsychiatric disorders (not only AD but also PD, schizophrenia and bipolar disorders) as very recently discussed by Sharma et al [ 249 ]. Other selenoproteins such as SelP, SelW and the ER-resident selenoproteins K, T, M (SelK, SelT, SelM) have been suggested to play pivotal roles in the brain [ 250 ]. Selenoproteins in the brain may act as antioxidants using either glutathione or thioredoxin as substrates.…”

Characterization and Quantification of Selenoprotein P: Challenges to Mass Spectrometry

“…During the last 40 years, many functions have been attributed to SELENOP including its involvement in the storage of selenium in the brain, testis [23,31] and kidney [32], defence against oxidative stress [33], loss of fertility [23], polycystic ovary syndrome [34] or regulation of heavy metals concentration [35,36]. SELENOP was reported to play a role in the potential development of various forms of cancer [37][38][39][40] and to be associated with neurodegenerative diseases such as Alzheimer's [39,[41][42][43]. SELENOP was evoked as a therapeutic target for type 2 diabetes [41,[44][45][46] because of its role in the regulation of glucose metabolism and insulin sensitivity.…”

Selenoproteome Expression Studied by Non-Radioactive Isotopic Selenium-Labeling in Human Cell Lines

“…The vital role of the essential trace element selenium (Se) in human health has been widely reported. Selenium deficiency is often evoked in the context of cancer, cardiac function, muscular disorders, infections, neurodegenerative disease, and aging [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Despite the essential nature of selenium, the range of its optimal intake is quite narrow and its toxicity can be quite easily achieved depending on its chemical speciation.…”