Synergistic neuroprotective effects of thiamine, pyridoxine and cyanocobalamin on the level of human proteome

Group B vitamins are characterized by neuroprotective effects. Mechanisms of action of synergistic combinations of various vitamins are insufficiently studied. In this study, proteins with activity or levels dependent on vitamins B₁ (thiamine), B₆ (pyridoxine) and B₁₂ (cyanocobalamin) were found in genomic and proteomic databases. Systems biology analysis showed that the thiamine is necessary for synthesis of ATP (glucose metabolism, lipid and branched chain amino acids), hemopoiesis and maintenance of neuronal structure. Pyridoxine-dependent proteins of the proteome are necessary for the metabolism of amino acids, ATP synthesis, synthesis of neurotransmitters and of neuronal membranes. Vitamin B₁₂ is needed for the metabolism of lipids, hemopoiesis and shows neuroprotective and neurotrophic effects. We identified numerous synergistic interactions of vitamins B₁, B₆, B₁₂, at the molecular level, including the metabolism of amino acids, carbohydrates, lipids, forming structures of neurons, blood, ATP synthesis etc. The established mechanisms of vitamins B₁, B₆, B₁₂ synergy at the molecular level are of fundamental importance for neuroprotection and prevention of cerebrovascular disease.

тиамин, пиридоксин, цианокобаламин, синергизм, биоинформатика, нейропротекция, Нейробион, thiamine, pyridoxine, cyanocobalamin, synergy, bioinformatics, neuroprotection, Neurobion

1. Torshin I.Y., Gromova O.A. Magnesium and pyridoxine: fundamental studies and clinical practice. Nova Science Publ.; 2011; 196.

2. Ребров В.Г., Громова О.А. Витамины, макро- и микроэлементы. ГэотарМед, М.: 2008; 674.

3. Torshin I.Yu. Sensing the change from molecular genetics to personalized medicine. Nova Biomedical Books, NY, USA, 2009, In “Bioinformatics in the Post-Genomic Era” series, ISBN 1-60692-217-0.

4. Forny P., Froese D.S., Suormala T., Yue W.W., Baumgartner M.R. Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency. Hum Mutat. 2014 Dec; 35 (12): 1449-58.

5. Ambrosch A., Dierkes J., Lobmann R., Kuhne W., Konig W., Luley C., Lehnert H. Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus. Diabet Med. 2001; 18 (3): 185-192.

6. Midttun O., Hustad S., Schneede J., Vollset S.E., Ueland P.M. Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr. 2007; 86 (1): 131-138.

7. Bettendorff L., Wins P., Lesourd M. Subcellular localization and compartmentation of thiamine derivatives in rat brain. Biochim Biophys Acta. 1994; 1222 (1): 1-6.

8. Fournier H., Butterworth R.F. Effects of maternal thiamine deficiency on the development of thiamine-dependent enzymes in regions of the rat brain. Neurochem Int. 1989; 15 (4): 439-444.

9. Kimura S., Ohtuki N., Nezu A., Tanaka M., Takeshita S. Clinical and radiologic improvements in mitochondrial encephalomyelopathy following sodium dichloroacetate therapy. Brain Dev. 1997; 19 (8): 535-540.

10. Sterzel R.B., Semar M., Lonergan E.T., TreserG., Lange K. Relationship of nervous tissue transketolase to the neuropathy in chronic uremia. J Clin Invest. 1971; 50 (11): 2295-2304.

11. Roomi M.W., Ishaque A., Khan N.R., Eylar E.H. Glycoproteins and albumin in peripheral nerve myelin. J Neurochem. 1978; 31 (1): 375-379.

12. Oka T., Komori N., Kuwahata M., Okada M., Natori Y. Vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding protein in rat liver. Biochem J. 1995; 309 (Pt 1: 243-248.

13. Isola L.M., Zhou S.L., Kiang C.L., Stump D.D., Bradbury M.W., Berk P.D. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake. Proc Natl Acad Sci U S A. 1995; 92 (21): 9866-9870.

14. Almeida M.R, Mabasa L., Crane C., Park C.S., Venancio V.P, Bianchi M.L., Antunes L.M. Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring. Mol Nutr Food Res. 2016; 60 (7): 1615-24 doi.

15. Rai N.K., Ashok A., Rai A., Tripathi S., Nagar G.K., Mitra K., Bandyopadhyay S. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina. Toxicol Appl Pharmacol. 2013; 273 (2): 242-58 doi.

16. Castegna A., Palmieri L., Spera I., Porcelli V., Palmieri F., Fabis-Pedrini M.J., Kean R.B., Barkhouse D.A., CurtisM.T., HooperD.C. Oxidative stress and reduced glutamine synthetase activity in the absence of inflammation in the cortex of mice with experimental allergic encephalomyelitis. Neuroscience. 2011; 185: 97-105 doi.

17. Yang T.Y., Chang G.C., Hsu S.L., Huang Y.R., Chiu L.Y., Sheu G.T. Effect of folic acid and vitamin B12 on pemetrexed antifolate chemotherapy in nutrient lung cancer cells. Biomed Res Int. 2013;2013:389046. doi: 10.1155/2013/389046.

18. Bauer J.A., Morrison B.H., Grane R.W., Jacobs B.S., Dabney S., Gamero A.M., Carnevale K.A., Smith D.J., Drazba J., Seetharam B., Lindner D.J. Effects of interferon beta on transcobalamin II-receptor expression and antitumor activity of nitrosylcobalamin. J Natl Cancer Inst. 2002 Jul 3; 94 (13): 1010-9.

19. Shimizu N., Hamazoe R., Kanayama H., Maeta M., Koga S. Experimental study of antitumor effect of methyl-B12. Oncology. 1987; 44 (3): 169-73.