Selenoproteins in Nervous System Development and Function

Abstract

Selenoproteins are a distinct class of proteins that are characterized by the co-translational incorporation of selenium (Se) in the form of the 21st amino acid selenocysteine. Selenoproteins provide a key defense against oxidative stress, as many of these proteins participate in oxidation-reduction reactions neutralizing reactive oxygen species, where selenocysteine residues act as catalytic sites. Many selenoproteins are highly expressed in the brain and mouse knockout studies have determined that several are required for normal brain development. In parallel with these laboratory studies, recent reports of rare human cases with mutations in genes involved in selenoprotein biosynthesis have described individuals with an assortment of neurological problems that mirror those detailed in knockout mice. These deficits include impairments in cognition and motor function, seizures, hearing loss, and altered thyroid metabolism. Additionally, due to the fact that oxidative stress is a key feature of neurodegenerative disease, there is considerable interest in the therapeutic potential of selenium supplementation for human neurological disorders. Studies performed in cell culture and rodent models have demonstrated that selenium administration attenuates oxidative stress, prevents neurodegeneration, and counters cell signaling mechanisms known to be dysregulated in certain disease states. However, there is currently no definitive evidence in support of selenium supplementation to prevent and/or treat common neurological conditions in the general population. It appears likely, that in humans, supplementation with selenium may only benefit certain subpopulations, such as those that are either selenium-deficient or possess genetic variants that affect selenium metabolism.

Maternal reproductive health: Expression patterns of antioxidant enzyme selenoproteins of post-implantation embryos conceived by ethanol-treated murine mothers supplemented with α-tocopherol

“…PHGPx, also known as GPx4, exhibits dynamic distribution in the brain during rat embryogenesis and that the three isoforms, mitochondrial (mGPx4), cytosolic (cGPx4) and nuclear (nGPx4) are highly expressed in the forebrain, midbrain and hindbrain regions during embryogenesis [8]. Hence, the presence of ethanol during the critical period of embryogenesis may most likely impact the expression of this selenoprotein enzyme in the developing brain.…”

“…Evidence showed that SelPP transported selenium to the brain [23] and it is claimed to be the main supplier of selenium to the brain [8] based on the report [24] that SelPP mRNA was homogeneously expressed in the mouse brain. Thus, SelPP is involved in maintaining a selenium pool in the brain that may prevent neurodegeneration.…”

“…Members of this family of proteins have roles in a variety of cell processes and diseases [7] and are key defense against oxidative stress where the selenocysteine residues serve as catalytic sites as they neutralize reactive oxygen species (ROS) [8]. Selenoproteins that are involved in antioxidant defense include the phospholipid hydroxyperoxide glutathione peroxidase (PHGPx) and Selenoprotein P (SelPP).…”

Biological functions of selenium and its potential influence on Parkinson's disease

“…The deletion of this protein causes inadequate uptake of Se by the brain, as demonstrated by Hill et al (2003) in a study using mice. More recently, other studies using animals showed that the deletion of selenoprotein P causes the degeneration of the brain cells (Caito et al 2011, Byrns et al 2014. By examining post mortem brain tissue from PD patients, Bellinger et al (2012) demonstrated that selenoprotein P expression decreased in the substantia nigra of these individuals compared with controls.…”

“…This value represents an amount of mineral approximately 4 times higher than the recommended value (can be used to evaluate the effects of high doses of the mineral) but much less than the amount that could pose a risk to health (IOM 2000, Ellwanger et al 2011, Yakubov et al 2014. Clinically, Se supplementation may be important for individuals from populations that live in geographical areas where the mineral is not easily consumed through diet or have genetic variations that alter the metabolism of the mineral (Pitts et al 2014). Methodological approaches using various animal models , Lu et al 2014 or cell cultures (Lamarche et al 2004, Maraldi et al 2011 are useful for answering questions related to the effects of Se on health/disease but cannot be investigated by testing in humans due to ethical and methodological reasons.…”