Skip to main content
SpringerLink
Log in

Selenium Neuroprotection in Neurodegenerative Disorders

  • Reference work entry
  • First Online:
Handbook of Neurotoxicity

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).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,299.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

3′-UTR:

3′-untranslated region

AChE:

Acetylcholinesterase

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

AREs:

Antioxidant response elements

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

Cys:

Cysteine

DFT:

Density functional theory

Dha:

Dehydroalanine

DIO1:

Iodothyronine deiodinase 1

DIO2:

Iodothyronine deiodinase 2

DIO3:

Iodothyronine deiodinase 3

DPDSe:

Diphenyl diselenide

EFSec:

Selenocysteine elongation factor

GPX:

Glutathione peroxidase

GPX1:

Glutathione peroxidase 1

GPX2:

Glutathione peroxidase 2

GPX3:

Glutathione peroxidase 3

GPX4:

Glutathione peroxidase 4

GPX6:

Glutathione peroxidase 6

GSH:

Reduced glutathione

GSSG:

Oxidized GSH

H2O:

Water

H2O2:

Hydrogen peroxide

H2SeO3:

Selenious acid

HgSe:

Mercury selenide

HS−:

Sulfide

HSe−:

Selenide

IL-1β:

Interleukin-1β

KEAP1:

Kelch-like ECH-associated protein 1

LMM-SH:

Low molecular mass thiol

MAO-A/B:

Monoamine oxidases A and B

MCI:

Mild cognitive impairment

mcm5U:

5-methoxycarbonylmethyluridine

mcm5Um:

5-5-methoxycarbonylmethyl-20-O-methyluridine

MeHg:

Methylmercury

MeSe•:

Methylselenyl

MeSec:

Methylselenocysteine

MeSeH:

Methylselenol

MSRB1:

Methionine sulfoxide reductase B1

NAS:

National Academy of Sciences

NFE2L2:

Nuclear factor, erythroid 2 like factor 2

NMD:

Nonsense-mediated decay

O:

Oxygen

PD:

Parkinson’s Disease

Po:

Polonium

PSTK:

Phosphoseryl-tRNA kinase

R′-SeH:

Selenol intermediates

RDA:

Recommended dietary allowance

REM:

Rapid eye movement

RNI:

Reference nutrient intake

ROOH:

Organic peroxides

ROS:

Reactive oxygen species

R-SeO2H:

Seleninic acid

S:

Sulfur

SBP2:

SECIS binding protein

Se:

Selenium

-Se=O:

Selenoxide

Sec:

Selenocysteine

SECIS:

Selenocysteine insertion sequence

-SeH:

Selenol

SELENOF:

Selenoprotein F

SELENOH:

Selenoprotein H

SELENOI:

Selenoprotein I

SELENOK:

Selenoprotein K

SELENOM:

Selenoprotein M

SELENON:

Selenoprotein N

SELENOO:

Selenoprotein O

SELENOP:

Selenoprotein P

SELENOS:

Selenoprotein S

SELENOT:

Selenoprotein T

SELENOV:

Selenoprotein V

SELENOW:

Selenoprotein W

SeM:

Selenomethionine

SeO3−2:

Selenite

−SeO3H:

Selenonic acid

SeO4−2:

Selenate

-Se-OH:

Selenenic acid

SEPHS2:

Selenophosphate synthase 2

SEPHS2:

Selenophosphate synthetase 2

SEPSecS:

Phosphoseryl-tRNA selenium transferase

Ser:

Serine

SerS:

Seryl-tRNA synthetase

-Se-S-:

Selenosulfide

T3:

Triiodothyronine

T4:

Thyroxine

Te:

Tellurium

TNF-α:

Tumor necrosis factor- α

TXNRD:

Thioredoxin reductase

TXNRD1:

Thioredoxin reductase 1

TXNRD2:

Thioredoxin reductase 2

TXNRD3:

Thioredoxin reductase 3

UL:

Upper intake level

α-syn:

α-synuclein

References

  • Adani, G., Filippini, T., Michalke, B., & Vinceti, M. (2020). Selenium and other trace elements in the etiology of Parkinson’s disease: A systematic review and meta-analysis of case-control studies. Neuroepidemiology, 54(1), 1–23. https://doi.org/10.1159/000502357

    Article  Google Scholar 

  • Ahmed, S., Mahmood, Z., & Zahid, S. (2015). Linking insulin with Alzheimer’s disease: Emergence as type III diabetes. Neurological Sciences, 36(10), 1763–1769. https://doi.org/10.1007/s10072-015-2352-5

    Article  Google Scholar 

  • Barbosa, N. V., Nogueira, C. W., Nogara, P. A., De Bem, A. F., Aschner, M., & Rocha, J. B. T. (2017). Organoselenium compounds as mimics of selenoproteins and thiol modifier agents. Metallomics, 9(12), 1703–1734. https://doi.org/10.1039/c7mt00083a

    Article  Google Scholar 

  • British Nutrition Foundation. (2001). Selenium and health. In British Nutrition Foundation (pp. 1–38). https://www.nutrition.org.uk/attachments/145_Seleniumandhealth.pdf

  • Bulteau, A.-L., & Chavatte, L. (2015). Update on selenoprotein biosynthesis. Antioxidants & Redox Signaling, 23(10), 775–794. https://doi.org/10.1089/ars.2015.6391

    Article  Google Scholar 

  • Burk, R. F., & Hill, K. E. (2005). Selenoprotein P: An extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annual Review of Nutrition, 25, 215–250. https://doi.org/10.1146/annurev.nutr.24.012003.132120

    Article  Google Scholar 

  • Byrns, C. N., Pitts, M. W., Gilman, C. A., Hashimoto, A. C., & Berry, M. J. (2014). Mice lacking selenoprotein P and selenocysteine lyase exhibit severe neurological dysfunction, neurodegeneration, and audiogenic seizures. Journal of Biological Chemistry, 289(14), 9662–9674. https://doi.org/10.1074/jbc.M113.540682

    Article  Google Scholar 

  • Caito, S. W., Milatovic, D., Hill, K. E., Aschner, M., Burk, R. F., & Valentine, W. M. (2011). Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted. Brain Research, 1398, 1–12. https://doi.org/10.1016/j.brainres.2011.04.046

    Article  Google Scholar 

  • Cardoso, B. R., Apolinário, D., Bandeira, V. S., Busse, A. L., Magaldi, R. M., Jacob-Filho, W., & Cozzolino, S. M. (2016). Effects of Brazil nut consumption on selenium status and cognitive performance in older adults with mild cognitive impairment: A randomized controlled pilot trial. European Journal of Nutrition, 55(1), 107–116. https://doi.org/10.1007/s00394-014-0829-2

    Article  Google Scholar 

  • Cardoso, B. R., Hare, D. J., Bush, A. I., Li, Q. X., Fowler, C. J., Masters, C. L., Martins, R. N., Ganio, K., Lothian, A., Mukherjee, S., Kapp, E. A., & Roberts, B. R. (2017). Selenium levels in serum, red blood cells, and cerebrospinal fluid of Alzheimer’s disease patients: A report from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL). Journal of Alzheimer’s Disease, 57(1), 183–193. https://doi.org/10.3233/JAD-160622

    Article  Google Scholar 

  • Cardoso, B. R., Roberts, B. R., Malpas, C. B., Vivash, L., Genc, S., Saling, M. M., Desmond, P., Steward, C., Hicks, R. J., Callahan, J., Brodtmann, A., Collins, S., Macfarlane, S., Corcoran, N. M., Hovens, C. M., Velakoulis, D., O’Brien, T. J., Hare, D. J., & Bush, A. I. (2019). Supranutritional sodium selenate supplementation delivers selenium to the central nervous system: Results from a randomized controlled pilot trial in Alzheimer’s disease. Neurotherapeutics, 16(1), 192–202. https://doi.org/10.1007/s13311-018-0662-z

    Article  Google Scholar 

  • Chawla, R., Filippini, T., Loomba, R., Cilloni, S., Dhillon, K. S., & Vinceti, M. (2020). Exposure to a high selenium environment in Punjab, India: Biomarkers and health conditions. Science of the Total Environment, 719, 134541. https://doi.org/10.1016/j.scitotenv.2019.134541

    Article  Google Scholar 

  • Chiò, A., Logroscino, G., Traynor, B. J., Collins, J., Simeone, J. C., Goldstein, L. A., & White, L. A. (2013). Global epidemiology of amyotrophic lateral sclerosis: A systematic review of the published literature. Neuroepidemiology, 41(2), 118–130. https://doi.org/10.1159/000351153

    Article  Google Scholar 

  • Chohan, H., Senkevich, K., Patel, R. K., Bestwick, J. P., Jacobs, B. M., Bandres Ciga, S., Gan-Or, Z., & Noyce, A. J. (2021). Type 2 diabetes as a determinant of Parkinson’s disease risk and progression. Movement Disorders. https://doi.org/10.1002/mds.28551

  • Cicero, C. E., Mostile, G., Vasta, R., Rapisarda, V., Signorelli, S. S., Ferrante, M., Zappia, M., & Nicoletti, A. (2017). Metals and neurodegenerative diseases. A systematic review. Environmental Research, 159, 82–94. https://doi.org/10.1016/j.envres.2017.07.048

    Article  Google Scholar 

  • Eratne, D., Loi, S. M., Farrand, S., Kelso, W., Velakoulis, D., & Looi, J. C. (2018). Alzheimer’s disease: Clinical update on epidemiology, pathophysiology and diagnosis. Australasian Psychiatry, 26(4), 347–357. https://doi.org/10.1177/1039856218762308

    Article  Google Scholar 

  • Filippini, T., Michalke, B., Wise, L. A., Malagoli, C., Malavolti, M., Vescovi, L., Salvia, C., Bargellini, A., Sieri, S., Krogh, V., Ferrante, M., & Vinceti, M. (2018). Diet composition and serum levels of selenium species: A cross-sectional study. Food and Chemical Toxicology, 115, 482–490. https://doi.org/10.1016/j.fct.2018.03.048

    Article  Google Scholar 

  • Fox, T. E., Van den Heuvel, E. G. H. M., Atherton, C. A., Dainty, J. R., Lewis, D. J., Langford, N. J., Crews, H. M., Luten, J. B., Lorentzen, M., Sieling, F. W., van Aken-Schneyder, P., Hoek, M., Kotterman, M. J. J., van Dael, P., & Fairweather-Tait, S. J. (2004). Bioavailability of selenium from fish, yeast and selenate: A comparative study in humans using stable isotopes. European Journal of Clinical Nutrition, 58(2), 343–349. https://doi.org/10.1038/sj.ejcn.1601787

    Article  Google Scholar 

  • Hardiman, O., Al-Chalabi, A., Chio, A., Corr, E. M., Logroscino, G., Robberecht, W., Shaw, P. J., Simmons, Z., & van den Berg, L. H. (2017). Amyotrophic lateral sclerosis. Nature Reviews Disease Primers, 3, 17071. https://doi.org/10.1038/nrdp.2017.71

    Article  Google Scholar 

  • Hariharan, S., & Dharmaraj, S. (2020). Selenium and selenoproteins: it’s role in regulation of inflammation. Inflammopharmacology, 28, 667–695. https://doi.org/10.1007/s10787-020-00690-x

    Article  Google Scholar 

  • Hatfield, D. L., Carlson, B. A., Xu, X.-M., Mix, H., & Gladyshev, V. N. (2006). Selenocysteine incorporation machinery and the role of selenoproteins in development and health. Progress in Nucleic Acid Research and Molecular Biology, 81, 97–142. https://doi.org/10.1016/S0079-6603(06)81003-2

    Article  Google Scholar 

  • Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015). Immune attack: The role of inflammation in Alzheimer disease. Nature Reviews Neuroscience, 16(6), 358–372. https://doi.org/10.1038/nrn3880

    Article  Google Scholar 

  • Institute of Medicine (US). (2000). Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. The National Academies Press (US).

    Google Scholar 

  • Jellinger, K. A. (2009). Recent advances in our understanding of neurodegeneration. Journal of Neural Transmission, 116(9), 1111–1162. https://doi.org/10.1007/s00702-009-0240-y

    Article  Google Scholar 

  • Ji, D., Wu, X., Li, D., Liu, P., Zhang, S., Gao, D., Gao, F., Zhang, M., & Xiao, Y. (2020). Protective effects of chondroitin sulphate nano-selenium on a mouse model of Alzheimer’s disease. International Journal of Biological Macromolecules, 154, 233–245. https://doi.org/10.1016/j.ijbiomac.2020.03.079

    Article  Google Scholar 

  • Kasaikina, M. V., Fomenko, D. E., Labunskyy, V. M., Lachke, S. A., Qiu, W., & Moncaster, J. A. (2011). Roles of the 15-kDa selenoprotein (Sep15) in redox homeostasis and cataract development revealed by the analysis of Sep 15 knockout mice. Journal of Biological Chemistry, 286, 33203–33212. https://doi.org/10.1074/jbc.M111.259218

    Article  Google Scholar 

  • Kiełczykowska, M., Kocot, J., Paździor, M., & Musik, I. (2018). Selenium – A fascinating antioxidant of protective properties. Advances in Clinical and Experimental Medicine, 27(2), 245–255. https://doi.org/10.17219/acem/67222

    Article  Google Scholar 

  • Kieliszek, M., & Błazejak, S. (2016). Current knowledge on the importance of selenium in food for living organisms: A review. Molecules, 10(5), 609. https://doi.org/10.3390/molecules21050609

    Article  Google Scholar 

  • Kühbacher, M., Bartel, J., Hoppe, B., Alber, D., Bukalis, G., Bräuer, A. U., Behne, D., & Kyriakopoulos, A. (2009). The brain selenoproteome: Priorities in the hierarchy and different levels of selenium homeostasis in the brain of selenium-deficient rats. Journal of Neurochemistry, 110(1), 133–142. https://doi.org/10.1111/j.1471-4159.2009.06109.x

    Article  Google Scholar 

  • LoPachin, R. M., Gavin, T., & Barber, D. S. (2008). Type-2 alkenes mediate synaptotoxicity in neurodegenerative diseases. Neurotoxicology, 29, 871–882. https://doi.org/10.1016/j.neuro.2008.04.016

    Article  Google Scholar 

  • Ma, S., Caprioli, R. M., Hill, K. E., & Burk, R. F. (2003). Loss of selenium from selenoproteins: Conversion of selenocysteine to dehydroalanine in vitro. Journal of the American Society for Mass Spectrometry, 14, 593–600. https://doi.org/10.1016/S1044-0305(03)00141-7

    Article  Google Scholar 

  • Maass, F., Michalke, B., Willkommen, D., Schulte, C., Tönges, L., Boerger, M., Zerr, I., Bähr, M., & Lingor, P. (2020). Selenium speciation analysis in the cerebrospinal fluid of patients with Parkinson’s disease. Journal of Trace Elements in Medicine and Biology, 57, 126412. https://doi.org/10.1016/j.jtemb.2019.126412

    Article  Google Scholar 

  • Marie, E. J., Wehrle, R. J., Haupt, D. J., Wood, N. B., Van Der Vliet, A., Previs, M. J., Masterson, D. S., & Hondal, R. J. (2020). Can selenoenzymes resist electrophilic modification? Evidence from thioredoxin reductase and a mutant containing α-methylselenocysteine. Biochemistry, 59, 3300–3315. https://doi.org/10.1021/acs.biochem.0c00608

    Article  Google Scholar 

  • Nogara, P. A., Oliveira, C. S., Schmitz, G. L., Piquini, P. C., Farina, M., Aschner, M., & Rocha, J. B. T. (2019). Methylmercury’s chemistry: From the environment to the mammalian brain. Biochimica et Biophysica Acta – General Subjects, 1863(12), 129284. https://doi.org/10.1016/j.bbagen.2019.01.006

    Article  Google Scholar 

  • Nogueira, C. W., Barbosa, N. V., & Rocha, J. B. T. (2021). Toxicology and pharmacology of synthetic organoselenium compounds: An update. Archives of Toxicology, 95, 1179–1226. https://doi.org/10.1007/s00204-021-03003-5

    Article  Google Scholar 

  • Oliveira, C. S., Piccoli, B. C., Aschner, M., & Rocha, J. B. T. (2017). Chemical speciation of selenium and mercury as determinant of their neurotoxicity. In M. Aschner & L. Costa (Eds.), Neurotoxicity of metals (Advances in neurobiology) (Vol. 18, pp. 53–83). Springer. https://doi.org/10.1007/978-3-319-60189-2_4

    Chapter  Google Scholar 

  • Orian, L., Mauri, P., Roveri, A., Toppo, S., Benazzi, L., Bosello-Travain, V., De Palma, A., Maiorino, M., Miotto, G., Zaccarin, M., Polimeno, A., Flohé, L., & Ursini, F. (2015). Selenocysteine oxidation in glutathione peroxidase catalysis: An MS-supported quantum mechanics study. Free Radical Biology and Medicine, 87, 1–14. https://doi.org/10.1016/j.freeradbiomed.2015.06.011

    Article  Google Scholar 

  • Pavlidou, E., Salpietro, V., Phadke, R., Hargreaves, I. P., Batten, L., McElreavy, K., Pitt, M., Mankad, K., Wilson, C., Cutrupi, M. C., Ruggieri, M., McCormick, D., Saggar, A., & Kinali, M. (2016). Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency. European Journal of Paediatric Neurology, 20(3), 483–488. https://doi.org/10.1016/j.ejpn.2015.12.016

    Article  Google Scholar 

  • Pitts, M. W., Reeves, M. A., Hashimoto, A. C., Ogawa, A., Kremer, P., Seale, L. A., & Berry, M. J. (2013). Deletion of selenoprotein M leads to obesity without cognitive deficits. Journal of Biological Chemistry, 288(36), 26121–26134. https://doi.org/10.1074/jbc.M113.471235

    Article  Google Scholar 

  • Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., Schrag, A. E., & Lang, A. E. (2017). Parkinson disease. Nature Reviews Disease Primers, 3, 17013. https://doi.org/10.1038/nrdp.2017.13

    Article  Google Scholar 

  • Raman, A. V., Pitts, M. W., Seyedali, A., Hashimoto, A. C., Bellinger, F. P., & Berry, M. J. (2013). Selenoprotein W expression and regulation in mouse brain and neurons. Brain and Behavior, 3(5), 562–574. https://doi.org/10.1002/brb3.159

    Article  Google Scholar 

  • Rayman, M. P., Winther, K. H., Pastor-Barriuso, R., Cold, F., Thvilum, M., Stranges, S., Guallar, E., & Cold, S. (2018). Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial. Free Radical Biology and Medicine, 127, 46–54. https://doi.org/10.1016/j.clnesp.2019.07.002

    Article  Google Scholar 

  • Reddy, V. S., Bukke, S., Dutt, N., Rana, P., & Pandey, A. K. (2017). A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer’s disease: A metal meta-analysis (AMMA study-I). Journal of Trace Elements in Medicine and Biology, 42, 68–75. https://doi.org/10.1016/j.jtemb.2017.04.005

    Article  Google Scholar 

  • Scheltens, P., Blennow, K., Breteler, M. M., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016). Alzheimer’s disease. Lancet, 388(10043), 505–517. https://doi.org/10.1016/S0140-6736(15)01124-1

    Article  Google Scholar 

  • Sheikh, S., Safia, Haque, E., & Mir, S. S. (2013). Neurodegenerative diseases: Multifactorial conformational diseases and their therapeutic interventions. Journal of Neurodegenerative Diseases, 2013, 563481. https://doi.org/10.1155/2013/563481

    Article  Google Scholar 

  • Tobe, R., & Mihara, H. (2018). Delivery of selenium to selenophosphate synthetase for selenoprotein biosynthesis. Biochimica et Biophysica Acta (BBA)-General Subjects, 1862(11), 2433–2440. https://doi.org/10.1016/j.bbagen.2018.05.023

    Article  Google Scholar 

  • Turanov, A. A., Xu, X.-M., Carlson, B. A., Yoo, M.-H., Gladyshev, V. N., & Hatfield, D. L. (2011). Biosynthesis of selenocysteine, the 21st amino acid in the genetic code, and a novel pathway for cysteine biosynthesis. Advances in Nutrition, 2, 122–128. https://doi.org/10.3945/an.110.000265

    Article  Google Scholar 

  • Valentine, W. M., Abel, T. W., Hill, K. E., Austin, L. M., & Burk, R. F. (2008). Neurodegeneration in mice resulting from loss of functional selenoprotein P or its receptor apolipoprotein E receptor 2. Journal of Neuropathology and Experimental Neurology, 67(1), 68–77. https://doi.org/10.1097/NEN.0b013e318160f347

    Article  Google Scholar 

  • Van Dijk, T., Vermeij, J. D., van Koningsbruggen, S., Lakeman, P., Baas, F., & Poll-The, B. T. (2018). A SEPSECS mutation in a 23-year-old woman with microcephaly and progressive cerebellar ataxia. Journal of Inherited Metabolic Disease, 41(5), 897–898. https://doi.org/10.1007/s10545-018-0151-x

    Article  Google Scholar 

  • Vendeland, S. C., Butler, J. A., & Whanger, P. D. (1992). Intestinal absorption of selenite, selenate, and selenomethionine in the rat. The Journal of Nutritional Biochemistry, 3(7), 359–365. https://doi.org/10.1016/0955-2863(92)90028-H

    Article  Google Scholar 

  • Verma, S., Hoffmann, F. W., Kumar, M., Huang, Z., Roe, K., Nguyen-Wu, E., Hashimoto, A. S., & Hoffmann, P. R. (2011). Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses. Journal of Immunology, 186(4), 2127–2137. https://doi.org/10.4049/jimmunol.1002878

    Article  Google Scholar 

  • Vinceti, M., Guidetti, D., Pinotti, M., Rovesti, S., Merlin, M., Vescovi, L., Bergomi, M., & Vivoli, G. (1996). Amyotrophic lateral sclerosis after long-term exposure to drinking water with high selenium content. Epidemiology, 7(5), 529–532.

    Article  Google Scholar 

  • Vinceti, M., Solovyev, N., Mandrioli, J., Crespi, C. M., Bonvicini, F., Arcolin, E., Georgoulopoulou, E., & Michalke, B. (2013). Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite. Neurotoxicology, 38, 25–32. https://doi.org/10.1016/j.neuro.2013.05.016

    Article  Google Scholar 

  • Vinceti, M., Mandrioli, J., Borella, P., Michalke, B., Tsatsakis, A., & Finkelstein, Y. (2014). Selenium neurotoxicity in humans: Bridging laboratory and epidemiologic studies. Toxicology Letters, 230(2), 295–303.

    Article  Google Scholar 

  • Vinceti, M., Chiari, A., Eichmüller, M., Rothman, K. J., Filippini, T., Malagoli, C., Weuve, J., Tondelli, M., Zamboni, G., Nichelli, P. F., & Michalke, B. (2017). A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment. Alzheimer’s Research & Therapy, 9(1), 100. https://doi.org/10.1186/s13195-017-0323-1

    Article  Google Scholar 

  • Vinceti, M., Michalke, B., Malagoli, C., Eichmüller, M., Filippini, T., Tondelli, M., Bargellini, A., Vinceti, G., Zamboni, G., & Chiari, A. (2019a). Selenium and selenium species in the etiology of Alzheimer’s dementia: The potential for bias of the case-control study design. Journal of Trace Elements in Medicine and Biology, 53, 154–162. https://doi.org/10.1016/j.jtemb.2019.03.002

    Article  Google Scholar 

  • Vinceti, M., Chawla, R., Filippini, T., Dutt, C., Cilloni, S., Loomba, R., Bargellini, A., Orsini, N., Dhillon, K. S., & Whelton, P. (2019b). Blood pressure levels and hypertension prevalence in a high selenium environment: Results from a cross-sectional study. Nutrition, Metabolism and Cardiovascular Diseases, 29(4), 398–408. https://doi.org/10.1016/j.numecd.2019.01.004

    Article  Google Scholar 

  • Vinceti, M., Filippini, T., Malagoli, C., Violi, F., Mandrioli, J., Consonni, D., Rothman, K. J., & Wise, L. A. (2019c). Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water: A long-term follow-up. Environmental Research, 179, 1–6. https://doi.org/10.1016/j.envres.2019.108742

    Article  Google Scholar 

  • Wang, S. K., Weaver, J. D., Zhang, S., & Lei, X. G. (2011). Knockout of SOD1 promotes conversion of selenocysteine to dehydroalanine in murine hepatic GPX1 protein. Free Radical Biology and Medicine, 51(1), 197–204. https://doi.org/10.1016/j.freeradbiomed.2011.03.018

    Article  Google Scholar 

  • Wirth, E. K., Conrad, M., Winterer, J., Wozny, C., Carlson, B. A., Roth, S., Schmitz, D., Bornkamm, G. W., Coppola, V., Tessarollo, L., Schombure, L., Köhrle, J., Hateld, D. L., & Schweizer, U. (2010). Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration. The FASEB Journal, 24, 844–852. https://doi.org/10.1096/fj.09-143974

    Article  Google Scholar 

  • Zhang, Y., Zhou, Y., Schweizer, U., Savaskan, N. E., Hua, D., Kipnis, J., Hatfield, D. L., & Gladyshev, V. N. (2007). Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals. Journal of Biological Chemistry, 283(4), 2427–2438. https://doi.org/10.1074/jbc.M707951200

    Article  Google Scholar 

  • Zhang, Z. H., Chen, C., Jia, S. Z., Cao, X. C., Liu, M., Tian, J., Hoffmann, P. R., Xu, H. X., Ni, J. Z., & Song, G. L. (2020). Selenium restores synaptic deficits by modulating NMDA receptors and selenoprotein K in an Alzheimer’s disease model. Antioxidants and Redox Signaling. https://doi.org/10.1089/ars.2019.7990

  • Zupanic, A., Meplan, C., Huguenin, G. V. B., Hesketh, J. E., & Shanley, D. P. (2016). Modeling and gene knockdown to assess the contribution of nonsense-mediated decay, premature termination, and selenocysteine insertion to the selenoprotein hierarchy. RNA, 22, 1076–1084. https://doi.org/10.1261/rna.055749.115

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação Stricto Sensu em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Instituto de Pesquisa Pelé Pequeno Príncipe, Paraná, Brazil

    Cláudia Sirlene Oliveira, Meire Ellen Pereira & Katherine Athayde Teixeira de Carvalho

  2. Faculdades Pequeno Príncipe, Paraná, Brazil

    Cláudia Sirlene Oliveira, Meire Ellen Pereira & Katherine Athayde Teixeira de Carvalho

  3. Departamento de Bioquímica e Biologia Molecular, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Bruna Candia Piccoli, Pablo Andrei Nogara & João Batista Teixeira Rocha

  4. Laboratory of Molecular Dietetics, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

    Anatoly V. Skalny & Alexey A. Tinkov

  5. Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Yaroslavl, Russia

    Anatoly V. Skalny & Alexey A. Tinkov

  6. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA

    Michael Aschner

Authors
  1. Cláudia Sirlene Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruna Candia Piccoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pablo Andrei Nogara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meire Ellen Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katherine Athayde Teixeira de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anatoly V. Skalny
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alexey A. Tinkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael Aschner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. João Batista Teixeira Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, Quillen College of Medicine East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Oliveira, C.S. et al. (2022). Selenium Neuroprotection in Neurodegenerative Disorders. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-031-15080-7_238

Download citation

Publish with us

Policies and ethics

Search

Navigation