**6. Selenium in the brain and brain diseases**

Oxidative stress and generation of reactive oxygen species (ROS) are strongly implicated in a number of neuronal and neuromuscular disorders, including stroke and cerebrovascular disease, Alzheimer's disease, Parkinson's disease, familial amyotrophic lateral sclerosis, and Duchenne muscular dystrophy (Dexter et al. 1989a,b; Smith et al. 1991; Ragusa et al. 1997; Cornett et al. 1998b; Facchinetti et al. 1998; Sagara et al. 1998; Tan et al. 1998). Selenium is known to provide protection from ROS-induced cell damage, and the proposed mechanisms mainly invoke the functions of glutathione peroxidases (GPxs) and selenoprotein P (SelP).

Considerable evidence exists linking heavy metals to neurodegenerative diseases (Thompson et al. 1988; Deibel et al. 1996; Cuajungco and Lees 1997; Schionning et al. 1997; Cornett et al. 1998b; Ely 2001). Heavy metals trigger the conversion of hydrogen peroxide to hydroxyl radical through Fenton reaction. Selenium has long been known to function as an antidote to toxicity of heavy metals. Co-administration of selenium was reported to play a role in reducing the toxic effects of mercury as early as the 1970s (Koelman et al. 1973; Kosta et al. 1975). Among the selenoproteins, SelP has been reported in several studies to possess metal-binding function (see below). The GPxs might also detoxify heavy metals through their well-known function of eliminating peroxides (Figure 2).

**Figure 2.** Complementary actions of selenium (GSH-Px) in free radical formation and lipid peroxidation (from Para‐ ntainen et al., 1987)
