Journal of Alzheimers & Neurodegenerative Diseases Category: Clinical Type: Commentary

A Commentary about the Function of Selenoprotein SELENOK for the Prevention and Treatment of Alzheimer’s Disease

Xue-Lian Meng1, Run-dong Wang2, Tian-qi Qiu2 and Chang-Lan Chen3*
1 School Of Pharmaceutical Science, Research Center For Natural Product Pharmacy Of Liaoning Province, Liaoning University, Shenyang, China
2 School Of Pharmaceutical Science, Liaoning University, Shenyang, China
3 School Of Pharmaceutical Science, Liaoning University, 66 Chongshan Middle Road, Huanggu District, Shenyang 110036, China

*Corresponding Author(s):
Chang-Lan Chen
School Of Pharmaceutical Science, Liaoning University, 66 Chongshan Middle Road, Huanggu District, Shenyang 110036, China
Tel:+86-024-62202192,
Email:chenchanglanbio@aliyun.com

Received Date: Aug 31, 2019
Accepted Date: Sep 05, 2019
Published Date: Sep 12, 2019

Keywords

Selenoprotein; SELENOK; Microglial cells; Migration; Phagocytosis; Neurodegenerative diseases

COMMENTARY

The role of trace element selenium (Se) on the preventing and treating Alzheimer’s disease (AD) and other neurodegenerative diseases has been confirmed by many researchers and should be paid more attention[1].Most of the functions of selenium are achieved through selenoproteins, and 25 selenoproteins have been known existing in human proteome [2,3]. SELENOK (selenoprotein K, SELK) is an 11-kDa selenoprotein (there are 94 amino acid residues for human SELENOK and mouse SELENOK, mSELENOK) located on the endoplasmic reticulum (ER) and Golgi membrane [4,5]. Studies have shown that SELENOK plays an important role in promoting the effective Ca2+influx during the activation of T cells, neutrophils, macrophages and other immune cells, and provides new insight for the study of the molecular mechanism of dietary selenium to enhance the immune response[6,7]. Our studies suggest that SELENOK can increase cytosolic free Ca2+level of microglial cells by up-regulating the expression of IP3R, thus enhancing the migration and phagocytosis of microglial cells[8].Since SELENOK can interact with the SH3 domains of DHHC6, a palmitic acid acyltransferase, to catalyzing the palmitoylation of IP3R and improve its stable expression[9,10], therefore, SELENOK’s deficiency might leads to the low expression of IP3R due to the defect of its palmitoylation[9].To date, many other selenoproteins also show some functions for the prevention and/or treatment of AD. Studies by other researchers have found that SELENOP (selenoprotein P, SeP, SEPP1, SELP) can not only plays a unique role in maintaining the stability of selenium content in the brain by transferring selenium into brain tissues and nerve cells via ApoER2 (a member of the lipoprotein receptor family) on vascular endothelial cells[11]but also serves as a donor of selenium in the synthesis of other selenoproteins[1]. Some selenoproteins can prevent and/or treat AD through inhibiting oxidative stress in the brain tissue, keeping the state of protein, biological membrane and other material types (GPx1, GPx4 (glutathione peroxidases) [12],MSRB1 (methionine sulfoxidereductase B1) [13] and SELENOW (selenoprotein W, SELW, SEPW1)), [14]. Some other selenoproteins work through preventing endoplasmic reticulum stress (SELENOS (selenoprotein S, SELS, SEPS1, VIMP)) [15],inhibiting inflammation factors or preventing mitochondria peroxide and maintaining the function of mitochondria (TXNRD (thioredoxinreductase) [16]and SELENOH (selenoprotein H, SELH)) [17]. Some other selenoproteins perform functions through maintaining intracellular calcium homeostasis (SELENOM (selenoprotein M, SELM))[18]or combining with the metal ions (SELENOP and MSRB) [13,19]. Although researches on the relationship between selenoproteins and AD has made gratifying progress in recent years, the target and mechanism of different selenoproteins in AD still need to be further studied.

CONFLICTS OF INTEREST

These authors have no conflicts of interest to declare.

ACKNOWLEDGMENTS

This study was supported by the National Natural Science Foundation of China (No. 31371085 and No. 81503085), the Foundation of the Education Department of Liaoning Province of China (No. LYB201610), and the Foundation of the Department of Science and Technology of Liaoning Province of China (No. 20180551168 and No. 201601097). The authors are grateful to Dr. Byoung Jae, Lee (Seoul National University, Seoul, Republic of Korea) for providing help on the studies of the functions of SELENOK.

REFERENCES

  1. Nakayama A, Hill KE, Austin LM, Motley AK, Burk RF (2007) All regions of mouse brain are dependent on selenoprotein P for maintenance of selenium. J Nutr 137:690-693.
  2. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, et al. (2003) Characterization of mammalian selenoproteomes. Science 300:1439-1443.
  3. Reeves MA, Hoffmann PR (2009) The human selenoproteome: Recent insights into functions and regulation. Cell Mol Life Sci 66:2457-2478.
  4. Chen CL, Shim MS, Chung J, Yoo HS, Ha JM, et al. (2006) G-rich, a Drosophila selenoprotein, is a Golgi-resident type III membrane protein. BiochemBiophys Res Commun 348:1296-1301.
  5. Lu C, Qiu F, Zhou H, Peng Y, Hao W, et al. (2006) Identification and characterization of selenoprotein K: An antioxidant in cardiomyocytes. FEBS Lett 580:5189-5197.
  6. Verma S, Hoffmann FW, Kumar M, Huang Z, Roe K, et al. (2011) Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses. J Immunol 186:2127-2137.
  7. Huang Z, Hoffmann FW, Norton RL, Hashimoto AC, Hoffmann PR (2011) Selenoprotein K is a novel target of m-calpain, and cleavage is regulated by Toll-like receptor-induced calpastatin in macrophages. J BiolChem 286:34830-34838.
  8. Meng XL, Chen CL, Liu YY, Su SJ, Gou JM, et al. (2019) Selenoprotein SELENOK enhances the migration and phagocytosis of microglial Cells by increasing the cytosolic free Ca2+ level resulted from the up-regulation of IP3R. Neuroscience 406: 38-49.
  9. Fredericks GJ, Hoffmann FW, Rose AH, Osterheld HJ, Hess FM, et al. (2014) Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. ProcNatlAcadSci U S A 111:16478-16483.
  10. Zhou X, Yang W, Li J (2006) Ca2+- and protein kinase C-dependent signaling pathway for nuclear factor-kappaB activation, inducible nitric-oxide synthase expression, and tumor necrosis factor-alpha production in lipopolysaccharide-stimulated rat peritoneal macrophages. J BiolChem 281:31337-31347.
  11. Burk RF, Hill KE, Motley AK, Winfrey VP (2014) Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration. FASEB J 28: 3579-3588.
  12. Battin EE, Brumaghim J L (2009) Antioxidant activity of sulfur and selenium: A review of reactive oxygen species scavenging, glutathione peroxidase, and metal-binding antioxidant mechanisms. Cell BiochemBiophys 55:1-23.
  13. Chen P, Wang C, Ma X, Zhang Y, Liu Q, et al. (2013) Direct interaction of sele-noprotein R with clusterin and its possible role in Alzheimer’s disease. Plos One 8: 1-12.
  14. Jeon YH, Yong HP, Kwon JH, Lee JH, Kim IY (2013) Inhibition of 14-3-3 binding to Rictor of mTORC2 for Akt phosphorylation at Ser473 is regulated by selenoprotein W. BiochimBiophysActa 1833:2135-2142.
  15. Jang JK, Park KJ, Lee JH, Ko KY, Kang S, et al. (2017) Selenoprotein S is required for clearance of C99 through endoplasmic reticulum-associateddegradation. BiochemBiophys Res Commun 486:444-450.
  16. Kudin AP, Augustynek B, Lehmann AK, Kovács R, Kunz WS (2012) The contribution of thioredoxin-2 reductase and glutathione peroxidase to H(2)O(2) detoxification of rat brain mitochondria. BiochimBiophysActa1817: 1901-1906.
  17. Mendelev N, Mehta SL, Witherspoon S, He Q, Sexton JZ, et al.(2011) Upregulation of human selenoprotein H in murine hippocampal neuronal cells promotes mitochondrial biogenesis and functional performance. Mitochondrion 11:76-82.
  18. Reeves MA, Bellinger FP, Berry MJ (2010) Theneuroprotective functions of selenoprotein M and its role in cytosolic calcium regulation. Antioxid Redox Signal 12:809-818.
  19. Du X, Qiu S, Wang Z, Wang R, Wang C, et al. (2014)Direct interaction between selenoprotein P and tubulin. Int J MolSci 15: 10199-10214.

Citation: Meng XL, Wang RD, Qiu TQ, Chen CL (2019) A Commentary about the Function of Selenoprotein SELENOK for the Prevention and Treatment of Alzheimer’s Disease. J Alzheimers Neurodegener Dis 5: 027.

Copyright: © 2019  Xue-Lian Meng, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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