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Selenoproteins in Nervous System Development and Function

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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.

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Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

Cys:

Cysteine

DIO:

Iodothyronine deiodinase

EFSec:

Selenocysteine-specific elongation factor

ER:

Endoplasmic reticulum

GPx:

Glutathione peroxidase

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PD:

Parkinson’s disease

PV:

Parvalbumin

SBP2:

Selenocysteine insertion sequence-binding protein 2

Scly:

Selenocysteine lyase

Se:

Selenium

Sec:

Selenocysteine

SECIS:

Selenocysteine insertion sequence

SELENBP1:

Selenium-binding protein 1

SN:

Substantia nigra

SPS2:

Selenophosphate synthetase 2

T3 :

3,3′,5-Triiodothyronine

T4 :

Thyroxine

TSH:

Thyroid stimulating hormone

Txn:

Thioredoxin

Txnrd:

Thioredoxin reductase

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  1. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo St, Honolulu, HI, 96813, USA

    Matthew W. Pitts, China N. Byrns, Ashley N. Ogawa-Wong, Penny Kremer & Marla J. Berry

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  1. Matthew W. Pitts
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Pitts, M.W., Byrns, C.N., Ogawa-Wong, A.N. et al. Selenoproteins in Nervous System Development and Function. Biol Trace Elem Res 161, 231–245 (2014). https://doi.org/10.1007/s12011-014-0060-2

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