Selenium and selenoproteins in the brain and brain diseases

Abstract

Over the past three decades, selenium has been intensively investigated as an antioxidant trace element. It is widely distributed throughout the body, but is particularly well maintained in the brain, even upon prolonged dietary selenium deficiency. Changes in selenium concentration in blood and brain have been reported in Alzheimer's disease and brain tumors. The functions of selenium are believed to be carried out by selenoproteins, in which selenium is specifically incorporated as the amino acid, selenocysteine. Several selenoproteins are expressed in brain, but many questions remain about their roles in neuronal function. Glutathione peroxidase has been localized in glial cells, and its expression is increased surrounding the damaged area in Parkinson's disease and occlusive cerebrovascular disease, consistent with its protective role against oxidative damage. Selenoprotein P has been reported to possess antioxidant activities and the ability to promote neuronal cell survival. Recent studies in cell culture and gene knockout models support a function for selenoprotein P in delivery of selenium to the brain. mRNAs for other selenoproteins, including selenoprotein W, thioredoxin reductases, 15-kDa selenoprotein and type 2 iodothyronine deiodinase, are also detected in the brain. Future research directions will surely unravel the important functions of this class of proteins in the brain.

Selective Gene Expression in Magnocellular Neurons in Rat Supraoptic Nucleus

“…These include encephalopsin (ratio, 6.2) (Blackshaw and Snyder, 1999); guanine nucleotide binding protein, ␣ stimulating (ratio, 5.4), reported previously in the SON (Young et al, 1987); calreticulin (ratio, 3.8) (Burns et al, 1994;Dedhar et al, 1994;Platet et al, 2000), glutathione peroxidase 3 (ratio, 10) (Mirault et al, 1994;Chen and Berry, 2003), and Rho GDP dissociation inhibitor ␤ (ratio, 3.4) (Bito, 2003). All of these genes increased in expression more than twofold in the SON during hyperosmolar conditions (Table 3).…”

Dietary and tissue selenium in relation to methylmercury toxicity

“…In contrast to other amino acids, SeCys is not reused in subsequent cycles of protein synthesis, but must be degraded to release inorganic selenium for synthesis of SeCys that is specifically emplaced in the active sites of selenoenzymes (Hatfield et al, 2006). Several selenoenzymes perform apparently indispensable antioxidant functions in the brain and neuroendocrine system (Chen and Berry, 2003;Schweizer et al, 2004;Whanger, 2001;Kohrle et al, 2000Kohrle et al, , 2005 and some have newly described functions (Ferguson et al, 2006;Novoselov et al, 2007;Dikiy et al, 2007) including redox control of an abundant class of brain proteins. These functions appear to explain why all forms of animal life that possess nervous systems also express and selectively preserve selenoenzyme activities in brain and neuroendocrine tissues (Behne et al, 2000;Sun et al, 2001).…”

Selenium as a Potential Protective Factor Against Mercury Developmental Neurotoxicity

“…Se is a constituent of selenoproteins, which are important antioxidant enzymes and catalyst for the production of active thyroid hormone (Rayman, 2000). Although the physiologic functions of Se in the brain are not well understood, studies have found that Se and certain selenoproteins are particularly well maintained despite prolonged Se deficiency, suggesting the important role of Se in this organ (Chen and Berry, 2003;Whanger, 2001). …”