Selenium Neuroprotection in Neurodegenerative Disorders

Abstract

Selenium (Se) is an essential element, and severe deficiency of Se is incompatible with human life. Se is part of a restricted group of 25 proteins, the selenoproteins. The selenoproteins have the rare amino acid selenocysteine (Sec), which is an analog of cysteine (Cys). The -SeH (selenol) group of Sec is an active redox center in selenoproteins, which are part of the endogenous antioxidant system, for instance, the oxidoreductases glutathione peroxidase (GPX) and thioredoxin reductase (TXNRD). The selenoproteins iodothyronine deiodinases (DIO1 and DIO2) are involved in the metabolism of triiodothyronine (T3) and thyroxine (T4) thyroid hormones; and methionine sulfoxide reductase B1 (MSRB1) reduces the oxidized methionine sulfoxide to methionine. Selenoprotein P (SELENOP) plays an important role in the body Se distribution and homeostasis. The brain is particularly dependent on Se supply via SELENOP and is spared from Se deficiency. Although Se deficiency can have neuropathological effects, the chronic exposure to Se levels above the nutritional requirement can be associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Paradoxically to Se role as antioxidant in the -SeH group of selenoproteins, the metabolites of Se in the body (particularly the selenide intermediates and methylselenol) are highly reactive and can generate cytotoxic prooxidant metabolites (e.g., methylselenyl radical). This chapter will explore the role of Se (both excess and deficiency) as physiological neuroprotective or neurotoxic agent potentially involved in chronic neurodegenerative pathologies, such as ALS, AD, and Parkinson’s disease (PD).