The human selenoproteome consists of 25 selenoproteins. The main groups are glutathione peroxidases 1-5, iodothyronine deiodinases 1-3, thioredoxin reductases, selenoprotein P (SelP), and other proteins mostly with unknown function. In selenoproteins selenium occurs as selenocysteine. SelP works as a transporter of selenium between the liver and other organs. Selenium in the form of selenomethionine can also unspecifically substitute for methionine in other proteins. In sheep and humans, Se is concentrated in tissues involved in the immune response, such as spleen, liver and lymph nodes.
The membrane-bound phospholipid hydroperoxide GPX (PHGPX) detoxifies phospholipid hydroperoxides and, along with vitamin E, helps prevent oxidative damage to membranes. The PHGPX may be more important than the cGPX in protecting the cell from oxidative stress. Elimination of peroxides in the extracellular fluid is dealt with by the extracellular or plasma form of GPX. The GPXs play a vital role in the synthesis of arachidonic acid metabolites. The lipoxygenase and cyclooxygenase pathways produce hydroperoxyeicosatetraenoic acids, which must be reduced for lipoxin, prostaglandin and leukotriene synthesis. Eicosanoid synthesis is depressed in Se deficiency. Furthermore, accumulation of lipoperoxides impairs prostacyclin synthesis and promotes thromboxane accumulation, which can increase platelet aggregation in cardiovascular disease. Other selenoproteins include the iodothyronine deiodinases (types I, II and III), which regulate the metabolism of thyroid hormones in all tissues. Clear functions are still being sought for other selenoproteins such as selenoprotein P and selenoprotein W. The former may be involved in Se transport; the latter is lost in Se-deficiencyinduced myopathy.
Accumulated lines of evidence indicate important roles of selenoproteins in the maintenance of optimal brain functions via redox regulation. Decreased expression of several selenoproteins is associated with the pathologies of a few age-associated neurodisorders, including Parkinson’s disease, Alzheimer’s disease and epilepsy. Recent advances using genetically manipulated mouse models demonstrate that selenoproteins offer protection against neurodegeneration primarily through redox regulation. Therapies targeting specific selenoproteins influencing redox regulation could delay the onset of neurodisorders, improve quality of life of patients already affected, and perhaps rescue patients with certain diseases by using novel gene therapies.