Selenium

Selenium (Se) is an enzymatic cofactor and an essential component of selenoaminoacids and selenoproteins. Se has numerous biological functions related to redox signaling, antioxidant defense systems, thyroid hormone metabolism, and humoral and cell-mediated immune responses [94]. Se reacts with redox signals involving one- or two-electron transitions; however, it is less reactive and prefers higher oxidation states. The biological activity of Se varies depending on its concentration: normal growth and development at low concentrations, homeostatic function at moderate concentrations, and induced toxicity at high concentrations [95]. The complex biological functions of Se are found in general body proteins that mainly and effectively act through 25 selenoproteins that have selenocysteine at their active center in humans [96]. Over half of the selenoproteins exhibit antioxidant activity, of which the GPx family and Trx reductase family are well known. Selenoproteins constrain the activation of nuclear factor-κB (NF-κB) via redox signaling, which prohibits a cytokine storm and the formation of reactive oxygen and nitrogen species. Se is essential for brain function, but the Se expression level in the brain is rather poor compared to other tissues [97,98]. The distribution of Se in the human brain enriched in gray matter tended to be higher, while the white matter was found to have reduced Se levels. Specifically, Se level was observed to be highest in the hippocampus, cerebellum, and brainstem in the rat brain [99]. The mechanism of Se neuroprotection is attributed to modulation of Ca2<sup>+</sup> influx via ion channels, anti-inflammatory effect by abrogation of microglia invasion, and biosynthesis stimulation of antioxidative selenoproteins in the brain [100,101].

Se is essential for the brain and plays an important role in the pathology of neuronal disorders such as AD, PD, ALS, and epilepsy [96]. In Se-deficient transgenic mice, Aβ plaques showed more than a two-fold increase compared to Se-adequate ones [102]. Selenite administration in a rat AD model also showed attenuation of cognitive deficits, oxidative damage and morphological changes in the hippocampus and cerebral cortex [103]. In a paraquat induced PD model, bradykinesia and DNA damage reduction were observed by supplementing Se with selenite in drinking water [104]. Alterations of Se homeostasis in the HD model have been observed and a beneficial effect of selenite supplementation in mice expressing mutant huntingtin has been reported. Additionally, autopsy of the human HD and mouse HD brain showed decreased Se content [105]. Selenite administration prevents secondary pathological events, thus, contributing to the reduction of apoptotic cell death and prevention of neuronal destruction in the cortex and hippocampus of traumatic brain injury [106,107]
