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The Role of Vitamin K in the Development of Neurodegenerative Diseases

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Abstract

Neurodegenerative diseases are a growing global health problem with enormous consequences for individuals and society. The most common neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, can be caused by both genetic factors (mutations) and epigenetic changes caused by the environment, in particular, oxidative stress. One of the factors contributing to the development of oxidative stress that has an important effect on the nervous system is vitamin K, which is involved in redox processes. However, its role in cells is ambiguous: accumulation of high concentrations of vitamin K increases the content of reactive oxygen species increases, while small amounts of vitamin K have a protective effect and activate the antioxidant defense systems. The main function of vitamin K is its involvement in the gamma carboxylation of the so-called Gla proteins. Some Gla proteins are expressed in the nervous system and participate in its development. Vitamin K deficiency can lead to a decrease or loss of function of Gla proteins in the nervous system. It is assumed that the level of vitamin K in the body is associated with specific changes involved in the development of dementia and cognitive abilities. Vitamin K also influences the sphingolipid profile in the brain, which also affects cognitive function. The role of vitamin K in the regulation of biochemical processes at the cellular and whole-organism levels has been studied insufficiently. Further research can lead to the discovery of new targets for vitamin K and development of personalized diets and therapies.

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Abbreviations

Aβ:

β-amyloid

GGC:

gamma-glutamyl carboxylase

MAPK:

mitogen-activated protein kinase

ROS:

reactive oxygen species

VKOR:

vitamin K epoxide reductase

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

References

  1. Itoh, S., and Iwaki, M. (1989) Vitamin K1 (Phylloquinone) restores the turnover of FeS centers in the ether-extracted spinach PS I particles, FEBS Lett., 243, 47-52, https://doi.org/10.1016/0014-5793(89)81215-3.

    Article  CAS  Google Scholar 

  2. Kurosu, M., and Begari, E. (2010) Vitamin K2 in electron transport system: are enzymes involved in vitamin K2 biosynthesis promising drug targets? Molecules, 15, 1531-1553, https://doi.org/10.3390/molecules15031531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bandyopadhyay, P. K., Garrett, J. E., Shetty, R. P., Keate, T., Walker, C. S., and Olivera, B. M. (2002) Gamma-glutamyl carboxylation: an extracellular posttranslational modification that antedates the divergence of molluscs, arthropods, and chordates, Proc. Natl. Acad. Sci. USA, 99, 1264-1269, https://doi.org/10.1073/pnas.022637099.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  4. Woollard, D. C., Indyk, H. E., Fong, B. Y., and Cook, K. K. (2002) Determination of vitamin K1 isomers in foods by liquid chromatography with C30 bonded-phase column, J. AOAC Int., 85, 682-691, https://doi.org/10.1093/jaoac/85.3.682.

    Article  CAS  PubMed  Google Scholar 

  5. Ayombil, F., and Camire, R. M. (2020) Insights into Vitamin K-dependent carboxylation: home field advantage, Haematologica, 105, 1996-1998, https://doi.org/10.3324/haematol.2020.253690.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kulman, J. D., Harris, J. E., Xie, L., and Davie, E. W. (2001) Identification of two novel transmembrane gamma-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues, Proc. Natl. Acad. Sci. USA, 98, 1370-1375, https://doi.org/10.1073/pnas.98.4.1370.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  7. Lee, T.-Y., Lu, C.-T., Chen, S.-A., Bretaña, N. A., Cheng, T.-H., Su, M.-G., and Huang, K.-Y. (2011) Investigation and identification of protein γ-glutamyl carboxylation sites, BMC Bioinformatics, 12, S10, https://doi.org/10.1186/1471-2105-12-S13-S10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Funakoshi, H., Yonemasu, T., Nakano, T., Matumoto, K., and Nakamura, T. (2002) Identification of Gas6, a putative ligand for Sky and Axl receptor tyrosine kinases, as a novel neurotrophic factor for hippocampal neurons, J. Neurosci. Res., 68, 150-160, https://doi.org/10.1002/jnr.10211.

    Article  CAS  PubMed  Google Scholar 

  9. Li, R., Chen, J., Hammonds, G., Phillips, H., Armanini, M., Wood, P., Bunge, R., Godowski, P. J., Sliwkowski, M. X., and Mather, J. P. (1996) Identification of Gas6 as a growth factor for human Schwann cells, J. Neurosci., 16, 2012-2019, https://doi.org/10.1523/JNEUROSCI.16-06-02012.1996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y. W., Hunt, R. W., Trail, G., Clogston, C., and Toso, R. J. (1995) Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6, Nature, 373, 623-626, https://doi.org/10.1038/373623a0.

    Article  CAS  PubMed  ADS  Google Scholar 

  11. Allen, M. P., Zeng, C., Schneider, K., Xiong, X., Meintzer, M. K., Bellosta, P., Basilico, C., Varnum, B., Heidenreich, K. A., and Wierman, M. E. (1999) Growth arrest-specific gene 6 (Gas6)/Adhesion Related Kinase (Ark) signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt, Mol. Endocrinol., 13, 191-201, https://doi.org/10.1210/mend.13.2.0230.

    Article  CAS  PubMed  Google Scholar 

  12. Allen, M. P., Linseman, D. A., Udo, H., Xu, M., Schaack, J. B., Varnum, B., Kandel, E. R., Heidenreich, K. A., and Wierman, M. E. (2002) Novel mechanism for gonadotropin-releasing hormone neuronal migration involving Gas6/Ark signaling to P38 mitogen-activated protein kinase, Mol. Cell. Biol., 22, 599-613, https://doi.org/10.1128/MCB.22.2.599-613.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ferland, G. (2012) Vitamin K and the nervous system: an overview of its actions, Adv. Nutr. (Bethesda, Md.), 3, 204-212, https://doi.org/10.3945/an.111.001784.

    Article  CAS  Google Scholar 

  14. Binder, M. D., Xiao, J., Kemper, D., Ma, G. Z. M., Murray, S. S., and Kilpatrick, T. J. (2011) Gas6 increases myelination by oligodendrocytes and its deficiency delays recovery following cuprizone-induced demyelination, PLoS One, 6, e17727, https://doi.org/10.1371/journal.pone.0017727.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  15. Matsushima, G. K., and Morell, P. (2001) The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system, Brain Pathol., 11, 107-116, https://doi.org/10.1111/j.1750-3639.2001.tb00385.x.

    Article  CAS  PubMed  Google Scholar 

  16. Tibrewal, N., Wu, Y., D’mello, V., Akakura, R., George, T. C., Varnum, B., and Birge, R. B. (2008) Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-κB transcriptional activation, J. Biol. Chem., 283, 3618-3627, https://doi.org/10.1074/jbc.M706906200.

    Article  CAS  PubMed  Google Scholar 

  17. Tanabe, K., Nagata, K., Ohashi, K., Nakano, T., Arita, H., and Mizuno, K. (1997) Roles of gamma-carboxylation and a sex hormone-binding globulin-like domain in receptor-binding and in biological activities of Gas6, FEBS Lett., 408, 306-310, https://doi.org/10.1016/s0014-5793(97)00448-1.

    Article  CAS  PubMed  Google Scholar 

  18. Bellido-Martín, L., and De Frutos, P. G. (2008) Vitamin K-dependent actions of Gas6, Vitam. Horm., 78, 185-209, https://doi.org/10.1016/S0083-6729(07)00009-X.

    Article  CAS  PubMed  Google Scholar 

  19. Liu, D., Guo, H., Griffin, J. H., Fernández, J. A., and Zlokovic, B. V. (2003) Protein S confers neuronal protection during ischemic/hypoxic injury in mice, Circulation, 107, 1791-1796, https://doi.org/10.1161/01.CIR.0000058460.34453.5A.

    Article  PubMed  Google Scholar 

  20. Liu, S., Li, S., Shen, G., Sukumar, N., Krezel, A. M., and Li, W. (2021) Structural basis of antagonizing the Vitamin K catalytic cycle for anticoagulation, Science, 371, https://doi.org/10.1126/science.abc5667.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ingram, B. O., Turbyfill, J. L., Bledsoe, P. J., Jaiswal, A. K., and Stafford, D. W. (2013) Assessment of the contribution of NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) to the reduction of vitamin K in wild-type and NQO1-deficient mice, Biochem. J., 456, 47-54, https://doi.org/10.1042/BJ20130639.

    Article  CAS  PubMed  Google Scholar 

  22. Porter, W. R. (2010) Warfarin: history, tautomerism and activity, J. Comput. Aided Mol. Design, 24, 553-573, https://doi.org/10.1007/s10822-010-9335-7.

    Article  CAS  ADS  Google Scholar 

  23. Lim, G. B. (2017) Milestone 2: warfarin: from rat poison to clinical use, Nat. Rev. Cardiol., https://doi.org/10.1038/nrcardio.2017.172.

    Article  PubMed  Google Scholar 

  24. Wu, S., Chen, X., Jin, D.-Y., Stafford, D. W., Pedersen, L. G., and Tie, J.-K. (2018) Warfarin and Vitamin K epoxide reductase: a molecular accounting for observed inhibition, Blood, 132, 647-657, https://doi.org/10.1182/blood-2018-01-830901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Czogalla, K. J., Biswas, A., Höning, K., Hornung, V., Liphardt, K., Watzka, M., and Oldenburg, J. (2017) Warfarin and Vitamin K compete for binding to Phe55 in human VKOR, Nat. Struct. Mol. Biol., 24, 77-85, https://doi.org/10.1038/nsmb.3338.

    Article  CAS  PubMed  Google Scholar 

  26. Matagrin, B., Hodroge, A., Montagut-Romans, A., Andru, J., Fourel, I., Besse, S., Benoit, E., and Lattard, V. (2013) New insights into the catalytic mechanism of Vitamin K epoxide reductase (VKORC1) – the catalytic properties of the major mutations of rVKORC1 explain the biological cost associated to mutations, FEBS Open Bio, 3, 144-150, https://doi.org/10.1016/j.fob.2013.02.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li, J., Zuo, X., Cheng, P., Ren, X., Sun, S., Xu, J., Holmgren, A., and Lu, J. (2019) The production of reactive oxygen species enhanced with the reduction of menadione by active thioredoxin reductase, Metallomics, 11, 1490-1497, https://doi.org/10.1039/c9mt00133f.

    Article  CAS  PubMed  Google Scholar 

  28. Majiene, D., Kuseliauskyte, J., Stimbirys, A., and Jekabsone, A. (2019) Comparison of the effect of native 1,4-naphthoquinones plumbagin, menadione, and lawsone on viability, redox status, and mitochondrial functions of C6 glioblastoma cells, Nutrients, 11, 1294, https://doi.org/10.3390/nu11061294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gerasimenko, J. V., Gerasimenko, O. V., Palejwala, A., Tepikin, A. V., Petersen, O. H., and Watson, A. J. M. (2002) Menadione-induced apoptosis: roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore, J. Cell Sci., 115, 485-497, https://doi.org/10.1242/jcs.115.3.485.

    Article  CAS  PubMed  Google Scholar 

  30. Shibayama-Imazu, T., Aiuchi, T., and Nakaya, K. (2008) Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential, Vitam. Horm., 78, 211-226, https://doi.org/10.1016/S0083-6729(07)00010-6.

    Article  CAS  PubMed  Google Scholar 

  31. Monteiro, J. P., Martins, A. F., Nunes, C., Morais, C. M., Lúcio, M., Reis, S., Pinheiro, T. J. T., Geraldes, C. F. G. C., Oliveira, P. J., and Jurado, A. S. (2013) A biophysical approach to menadione membrane interactions: relevance for menadione-induced mitochondria dysfunction and related deleterious/therapeutic effects, Biochim. Biophys. Acta, 1828, 1899-1908, https://doi.org/10.1016/j.bbamem.2013.04.006.

    Article  CAS  PubMed  Google Scholar 

  32. Kolbrink, B., von Samson-Himmelstjerna, F. A., Messtorff, M. L., Riebeling, T., Nische, R., Schmitz, J., Bräsen, J. H., Kunzendorf, U., and Krautwald, S. (2022) Vitamin K1 inhibits ferroptosis and counteracts a detrimental effect of phenprocoumon in experimental acute kidney injury, Cell. Mol. Life Sci., 79, 387, https://doi.org/10.1007/s00018-022-04416-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Blesa, J., Trigo-Damas, I., Quiroga-Varela, A., and Jackson-Lewis, V. R. (2015) Oxidative stress and Parkinson’s disease, Front. Neuroanat., 9, 91, https://doi.org/10.3389/fnana.2015.00091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dias, V., Junn, E., and Mouradian, M. M. (2013) The role of oxidative stress in Parkinson’s disease, J. Parkinson’s Disease, 3, 461-491, https://doi.org/10.3233/JPD-130230.

    Article  CAS  Google Scholar 

  35. Gu, F., Chauhan, V., and Chauhan, A. (2015) Glutathione redox imbalance in brain disorders, Curr. Opin. Clin. Nutr. Metab. Care, 18, 89-95, https://doi.org/10.1097/MCO.0000000000000134.

    Article  CAS  PubMed  Google Scholar 

  36. Johnson, W. M., Wilson-Delfosse, A. L., and Mieyal, John. J. (2012) Dysregulation of glutathione homeostasis in neurodegenerative diseases, Nutrients, 4, 1399-1440, https://doi.org/10.3390/nu4101399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Reichert, C. O., de Freitas, F. A., Sampaio-Silva, J., Rokita-Rosa, L., de Lima Barros, P., Levy, D., and Bydlowski, S. P. (2020) Ferroptosis mechanisms involved in neurodegenerative diseases, Int. J. Mol. Sci., 21, 8765, https://doi.org/10.3390/ijms21228765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Doll, S., Freitas, F. P., Shah, R., Aldrovandi, M., da Silva, M. C., Ingold, I., Goya Grocin, A., Xavier da Silva, T. N., Panzilius, E., Scheel, C. H., Mourão, A., Buday, K., Sato, M., Wanninger, J., Vignane, T., Mohana, V., Rehberg, M., Flatley, A., Schepers, A., Kurz, A., White, D., Sauer, M., Sattler, M., Tate, E. W., Schmitz, W., Schulze, A., O’Donnell, V., Proneth, B., Popowicz, G. M., Pratt, D. A., Angeli, J. P. F., and Conrad, M. (2019) FSP1 is a glutathione-independent ferroptosis suppressor, Nature, 575, 693-698, https://doi.org/10.1038/s41586-019-1707-0.

    Article  CAS  PubMed  ADS  Google Scholar 

  39. Kraft, V. A. N., Bezjian, C. T., Pfeiffer, S., Ringelstetter, L., Müller, C., Zandkarimi, F., Merl-Pham, J., Bao, X., Anastasov, N., Kössl, J., Brandner, S., Daniels, J. D., Schmitt-Kopplin, P., Hauck, S. M., Stockwell, B. R., Hadian, K., and Schick, J. A. (2020) GTP cyclohydrolases 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling, ACS Central Sci., 6, 41-53, https://doi.org/10.1021/acscentsci.9b01063.

    Article  CAS  Google Scholar 

  40. Seiler, A., Schneider, M., Förster, H., Roth, S., Wirth, E. K., Culmsee, C., Plesnila, N., Kremmer, E., Rådmark, O., Wurst, W., Bornkamm, G. W., Schweizer, U., and Conrad, M. (2008) Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death, Cell Metab., 8, 237-248, https://doi.org/10.1016/j.cmet.2008.07.005.

    Article  CAS  PubMed  Google Scholar 

  41. Soula, M., Weber, R. A., Zilka, O., Alwaseem, H., La, K., Yen, F., Molina, H., Garcia-Bermudez, J., Pratt, D. A., and Birsoy, K. (2020) Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers, Nat. Chem. Biol., 16, 1351-1360, https://doi.org/10.1038/s41589-020-0613-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li, W., Liang, L., Liu, S., Yi, H., and Zhou, Y. (2023) FSP1: a key regulator of ferroptosis, Trends Mol. Med., 29, 753-764, https://doi.org/10.1016/j.molmed.2023.05.013.

    Article  CAS  PubMed  Google Scholar 

  43. Mishima, E., Ito, J., Wu, Z., Nakamura, T., Wahida, A., Doll, S., Tonnus, W., Nepachalovich, P., Eggenhofer, E., Aldrovandi, M., Henkelmann, B., Yamada, K.-I., Wanninger, J., Zilka, O., Sato, E., Feederle, R., Hass, D., Maida, A., Mourão, A. S. D., Linkermann, A., Geissler, E. K., Nakagawa, K., Abe, T., Fedorova, M., Proneth, B., Pratt, D. A., and Conrad, M. (2022) A non-canonical Vitamin K cycle is a potent ferroptosis suppressor, Nature, 608, 778-783, https://doi.org/10.1038/s41586-022-05022-3.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  44. Li, J., Lin, J. C., Wang, H., Peterson, J. W., Furie, B. C., Furie, B., Booth, S. L., Volpe, J. J., and Rosenberg, P. A. (2003) Novel role of Vitamin K in preventing oxidative injury to developing oligodendrocytes and neurons, J. Neurosci., 23, 5816-5826, https://doi.org/10.1523/JNEUROSCI.23-13-05816.2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Booth, S. L., Shea, M. K., Barger, K., Leurgans, S. E., James, B. D., Holland, T. M., Agarwal, P., Fu, X., Wang, J., Matuszek, G., and Schneider, J. A. (2022) Association of Vitamin K with cognitive decline and neuropathology in community-dwelling older persons, Alzheimer’s Demen., 8, e12255, https://doi.org/10.1002/trc2.12255.

    Article  Google Scholar 

  46. Brangier, A., Ferland, G., Rolland, Y., Gautier, J., Féart, C., and Annweiler, C. (2018) Vitamin K antagonists and cognitive decline in older adults: a 24-month follow-up, Nutrients, 10, 666, https://doi.org/10.3390/nu10060666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Presse, N., Belleville, S., Gaudreau, P., Greenwood, C. E., Kergoat, M.-J., Morais, J. A., Payette, H., Shatenstein, B., and Ferland, G. (2013) Vitamin K status and cognitive function in healthy older adults, Neurobiol. Aging, 34, 2777-2783, https://doi.org/10.1016/j.neurobiolaging.2013.05.031.

    Article  CAS  PubMed  Google Scholar 

  48. Soutif-Veillon, A., Ferland, G., Rolland, Y., Presse, N., Boucher, K., Féart, C., and Annweiler, C. (2016) Increased dietary Vitamin K intake is associated with less severe subjective memory complaint among older adults, Maturitas, 93, 131-136, https://doi.org/10.1016/j.maturitas.2016.02.004.

    Article  CAS  PubMed  Google Scholar 

  49. Kiely, A., Ferland, G., Ouliass, B., O’Toole, P. W., Purtill, H., and O’Connor, E. M. (2020) Vitamin K status and inflammation are associated with cognition in older Irish adults, Nutrit. Neurosci., 23, 591-599, https://doi.org/10.1080/1028415X.2018.1536411.

    Article  CAS  Google Scholar 

  50. Morris, M. C., Wang, Y., Barnes, L. L., Bennett, D. A., Dawson-Hughes, B., and Booth, S. L. (2018) Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study, Neurology, 90, e214-e222, https://doi.org/10.1212/WNL.0000000000004815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tanprasertsuk, J., Ferland, G., Johnson, M. A., Poon, L. W., Scott, T. M., Barbey, A. K., Barger, K., Wang, X.-D., and Johnson, E. J. (2020) Concentrations of circulating phylloquinone, but not cerebral menaquinone-4, are positively correlated with a wide range of cognitive measures: exploratory findings in centenarians, J. Nutr., 150, 82-90, https://doi.org/10.1093/jn/nxz200.

    Article  PubMed  Google Scholar 

  52. Carrié, I., Bélanger, E., Portoukalian, J., Rochford, J., and Ferland, G. (2011) Lifelong low-phylloquinone intake is associated with cognitive impairments in old rats, J. Nutr., 141, 1495-1501, https://doi.org/10.3945/jn.110.137638.

    Article  CAS  PubMed  Google Scholar 

  53. James, B. D., Leurgans, S. E., Hebert, L. E., Scherr, P. A., Yaffe, K., and Bennett, D. A. (2014) Contribution of Alzheimer disease to mortality in the United States, Neurology, 82, 1045-1050, https://doi.org/10.1212/WNL.0000000000000240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yee, A., Tsui, N. B., Chang, Y. N., Au, C. S., Fok, M., Lau, L. T., Chung, T., Chung, G., Kwan, R. Y., Leung, A. Y., Lau, J. Y., and Dai, D. L. (2018) Alzheimer’s disease: insights for risk evaluation and prevention in the Chinese population and the need for a comprehensive programme in Hong Kong/China, Hong Kong Med. J., 24, 492-500, https://doi.org/10.12809/hkmj187244.

    Article  CAS  PubMed  Google Scholar 

  55. Belrose, J. C., and Noppens, R. R. (2019) Anesthesiology and cognitive impairment: a narrative review of current clinical literature, BMC Anesthesiol., 19, 241, https://doi.org/10.1186/s12871-019-0903-7.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Miao, H., Dong, Y., Zhang, Y., Zheng, H., Shen, Y., Crosby, G., Culley, D. J., Marcantonio, E. R., and Xie, Z. (2018) Anesthetic isoflurane or desflurane plus surgery differently affects cognitive function in Alzheimer’s disease transgenic mice, Mol. Neurobiol., 55, 5623-5638, https://doi.org/10.1007/s12035-017-0787-9.

    Article  CAS  PubMed  Google Scholar 

  57. Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., Berry, R., and Vassar, R. (2006) Intraneuronal β-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation, J. Neurosci., 26, 10129-10140, https://doi.org/10.1523/JNEUROSCI.1202-06.2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Yu, Y., Yang, Y., Tan, H., Boukhali, M., Khatri, A., Yu, Y., Hua, F., Liu, L., Li, M., Yang, G., Dong, Y., Zhang, Y., Haas, W., and Xie, Z. (2020) Tau contributes to sevoflurane-induced neurocognitive impairment in neonatal mice, Anesthesiology, 133, 595-610, https://doi.org/10.1097/ALN.0000000000003452.

    Article  CAS  PubMed  Google Scholar 

  59. Alam, P., Chaturvedi, S. K., Siddiqi, M. K., Rajpoot, R. K., Ajmal, M. R., Zaman, M., and Khan, R. H. (2016) Vitamin K3 inhibits protein aggregation: implication in the treatment of amyloid diseases, Sci. Rep., 6, 26759, https://doi.org/10.1038/srep26759.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  60. Hadipour, E., Tayarani-Najaran, Z., and Fereidoni, M. (2020) Vitamin K2 protects PC12 Cells against Aβ (1-42) and H2O2-induced apoptosis via P38 MAP kinase pathway, Nutrit. Neurosci., 23, 343-352, https://doi.org/10.1080/1028415X.2018.1504428.

    Article  CAS  Google Scholar 

  61. Huang, S.-H., Fang, S.-T., and Chen, Y.-C. (2021) Molecular mechanism of Vitamin K2 protection against amyloid-β-induced cytotoxicity, Biomolecules, 11, 423, https://doi.org/10.3390/biom11030423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lin, X., Wen, X., Wei, Z., Guo, K., Shi, F., Huang, T., Wang, W., and Zheng, J. (2021) Vitamin K2 protects against Aβ42-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila, Neuroreport, 32, 431-437, https://doi.org/10.1097/WNR.0000000000001599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Guin, D., Mishra, M. K., Talwar, P., Rawat, C., Kushwaha, S. S., Kukreti, S., and Kukreti, R. (2017) A systematic review and integrative approach to decode the common molecular link between levodopa response and Parkinson’s disease, BMC Med. Genomics, 10, 56, https://doi.org/10.1186/s12920-017-0291-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Simon, D. K., Tanner, C. M., and Brundin, P. (2020) Parkinson disease epidemiology, pathology, genetics, and pathophysiology, Clin. Geriatr. Med., 36, 1-12, https://doi.org/10.1016/j.cger.2019.08.002.

    Article  PubMed  Google Scholar 

  65. Ramesh, S. and Perera Molligoda Arachchige, A. S. (2023) Depletion of dopamine in Parkinson’s disease and relevant therapeutic options: a review of the literature, AIMS Neurosci., 10, 200-231, https://doi.org/10.3934/neuroscience.2023017.

    Article  PubMed  Google Scholar 

  66. Jankovic, J. (2008) Parkinson’s disease: clinical features and diagnosis, J. Neurol. Neurosurg. Psychiatry, 79, 368-376, https://doi.org/10.1136/jnnp.2007.131045.

    Article  CAS  PubMed  Google Scholar 

  67. Yu, Y.-X., Yu, X.-D., Cheng, Q.-Z., Tang, L., and Shen, M.-Q. (2020) The association of serum vitamin K2 levels with Parkinson’s disease: from basic case-control study to big data mining analysis, Aging, 12, 16410-16419, https://doi.org/10.18632/aging.103691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Karimi-Moghadam, A., Charsouei, S., Bell, B., and Jabalameli, M. R. (2018) Parkinson disease from mendelian forms to genetic susceptibility: new molecular insights into the neurodegeneration process, Cell. Mol. Neurobiol., 38, 1153-1178, https://doi.org/10.1007/s10571-018-0587-4.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Mehra, S., Sahay, S., and Maji, S. K. (2019) α-Synuclein misfolding and aggregation: implications in Parkinson’s disease pathogenesis, Biochim. Biophys. Acta Proteins Proteomics, 1867, 890-908, https://doi.org/10.1016/j.bbapap.2019.03.001.

    Article  CAS  PubMed  Google Scholar 

  70. Abugable, A. A., Morris, J. L. M., Palminha, N. M., Zaksauskaite, R., Ray, S., and El-Khamisy, S. F. (2019) DNA repair and neurological disease: from molecular understanding to the development of diagnostics and model organisms, DNA Repair, 81, 102669, https://doi.org/10.1016/j.dnarep.2019.102669.

    Article  CAS  PubMed  Google Scholar 

  71. Stefanis, L. (2012) α-Synuclein in Parkinson’s disease, Cold Spring Harbor Perspect. Med., 2, a009399, https://doi.org/10.1101/cshperspect.a009399.

    Article  CAS  Google Scholar 

  72. Da Silva, F. L., Coelho Cerqueira, E., de Freitas, M. S., Gonçalves, D. L., Costa, L. T., and Follmer, C. (2013) Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein, Neurochem. Int., 62, 103-112, https://doi.org/10.1016/j.neuint.2012.10.001.

    Article  CAS  PubMed  Google Scholar 

  73. Tan, E.-K., and Skipper, L. M. (2007) Pathogenic mutations in Parkinson disease, Hum. Mutat., 28, 641-653, https://doi.org/10.1002/humu.20507.

    Article  CAS  PubMed  Google Scholar 

  74. Prasuhn, J., Kasten, M., Vos, M., König, I. R., Schmid, S. M., Wilms, B., Klein, C., and Brüggemann, N. (2020) The use of vitamin K2 in patients with Parkinson’s disease and mitochondrial dysfunction (PD-K2): a theranostic pilot study in a placebo-controlled parallel group design, Front. Neurol., 11, 592104, https://doi.org/10.3389/fneur.2020.592104.

    Article  PubMed  Google Scholar 

  75. Vos, M., Esposito, G., Edirisinghe, J. N., Vilain, S., Haddad, D. M., Slabbaert, J. R., Van Meensel, S., Schaap, O., De Strooper, B., Meganathan, R., Morais, V. A., and Verstreken, P. (2012) Vitamin K2 is a mitochondrial electron carrier that rescues Pink1 deficiency, Science, 336, 1306-1310, https://doi.org/10.1126/science.1218632.

    Article  CAS  PubMed  ADS  Google Scholar 

  76. Yu, Y.-X., Li, Y.-P., Gao, F., Hu, Q.-S., Zhang, Y., Chen, D., and Wang, G.-H. (2016) Vitamin K2 suppresses rotenone-induced microglial activation in vitro, Acta Pharmacol. Sin., 37, 1178-1189, https://doi.org/10.1038/aps.2016.68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Oizumi, H., Sugimura, Y., Totsune, T., Kawasaki, I., Ohshiro, S., Baba, T., Kimpara, T., Sakuma, H., Hasegawa, T., Kawahata, I., Fukunaga, K., and Takeda, A. (2022) Plasma sphingolipid abnormalities in neurodegenerative diseases, PLoS One, 17, e0279315, https://doi.org/10.1371/journal.pone.0279315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Pujol-Lereis, L. M. (2019) Alteration of sphingolipids in biofluids: implications for neurodegenerative diseases, Int. J. Mol. Sci., 20, 3564, https://doi.org/10.3390/ijms20143564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Van Kruining, D., Luo, Q., Van Echten-Deckert, G., Mielke, M. M., Bowman, A., Ellis, S., Oliveira, T. G., and Martinez-Martinez, P. (2020) Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods, Adv. Drug Deliv. Rev., 159, 232-244, https://doi.org/10.1016/j.addr.2020.04.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Huby, E., Napier, J. A., Baillieul, F., Michaelson, L. V., and Dhondt-Cordelier, S. (2020) Sphingolipids: towards an integrated view of metabolism during the plant stress response, New Phytol., 225, 659-670, https://doi.org/10.1111/nph.15997.

    Article  PubMed  Google Scholar 

  81. Alisi, L., Cao, R., De Angelis, C., Cafolla, A., Caramia, F., Cartocci, G., Librando, A., and Fiorelli, M. (2019) The relationships between vitamin K and cognition: a review of current evidence, Front. Neurol., 10, 239, https://doi.org/10.3389/fneur.2019.00239.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Saller, F., Brisset, A. C., Tchaikovski, S. N., Azevedo, M., Chrast, R., Fernández, J. A., Schapira, M., Hackeng, T. M., Griffin, J. H., and Angelillo-Scherrer, A. (2009) Generation and phenotypic analysis of protein S-deficient mice, Blood, 114, 2307-2314, https://doi.org/10.1182/blood-2009-03-209031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. De Wit, N. M., Mol, K., Rodríguez-Lorenzo, S., de Vries, H. E., and Kooij, G. (2020) The role of sphingolipids and specialized pro-resolving mediators in Alzheimer’s disease, Front. Immunol., 11, 620348, https://doi.org/10.3389/fimmu.2020.620348.

    Article  CAS  PubMed  Google Scholar 

  84. Alaamery, M., Albesher, N., Aljawini, N., Alsuwailm, M., Massadeh, S., Wheeler, M. A., Chao, C., and Quintana, F. J. (2021) Role of sphingolipid metabolism in neurodegeneration, J. Neurochem., 158, 25-35, https://doi.org/10.1111/jnc.15044.

    Article  CAS  PubMed  Google Scholar 

  85. Alessenko, A. V., and Albi, E. (2020) Exploring sphingolipid implications in neurodegeneration, Front. Neurol., 11, 437, https://doi.org/10.3389/fneur.2020.00437.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Pan, X., Dutta, D., Lu, S., and Bellen, H. J. (2023) Sphingolipids in neurodegenerative diseases, Front. Neurosci., 17, 1137893, https://doi.org/10.3389/fnins.2023.1137893.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Sivasubramanian, M., Kanagaraj, N., Dheen, S. T., and Tay, S. S. W. (2015) Sphingosine kinase 2 and sphingosine-1-phosphate promotes mitochondrial function in dopaminergic neurons of mouse model of Parkinson’s disease and in MPP+-treated MN9D cells in vitro, Neuroscience, 290, 636-648, https://doi.org/10.1016/j.neuroscience.2015.01.032.

    Article  CAS  PubMed  Google Scholar 

  88. Lev, M., and Milford, A. F. (1973) The 3-ketodihydrosphingosine synthetase of bacteroides melaninogenicus: induction by vitamin K, Arch. Biochem. Biophys., 157, 500-508, https://doi.org/10.1016/0003-9861(73)90668-1.

    Article  CAS  PubMed  Google Scholar 

  89. Dheen, S. T., Kaur, C., and Ling, E.-A. (2007) Microglial activation and its implications in the brain diseases, Curr. Med. Chem., 14, 1189-1197, https://doi.org/10.2174/092986707780597961.

    Article  CAS  PubMed  Google Scholar 

  90. Lampron, A., Elali, A., and Rivest, S. (2013) Innate immunity in the CNS: redefining the relationship between the CNS and its environment, Neuron, 78, 214-232, https://doi.org/10.1016/j.neuron.2013.04.005.

    Article  CAS  PubMed  Google Scholar 

  91. Kim, S., Steelman, A. J., Zhang, Y., Kinney, H. C., and Li, J. (2012) Aberrant upregulation of astroglial ceramide potentiates oligodendrocyte injury, Brain Pathol., 22, 41-57, https://doi.org/10.1111/j.1750-3639.2011.00501.x.

    Article  CAS  PubMed  Google Scholar 

  92. Denisova, N. A., and Booth, S. L. (2005) Vitamin K and sphingolipid metabolism: evidence to date, Nutrit. Rev., 63, 111-121, https://doi.org/10.1111/j.1753-4887.2005.tb00129.x.

    Article  PubMed  Google Scholar 

  93. Lev, M. (1958) Apparent requirement for Vitamin K of rumen strains of fusiformis nigrescens, Nature, 181, 203-204, https://doi.org/10.1038/181203a0.

    Article  CAS  PubMed  ADS  Google Scholar 

  94. Sundaram, K. S., and Lev, M. (1988) Warfarin administration reduces synthesis of sulfatides and other sphingolipids in mouse brain, J. Lipid Res., 29, 1475-1479, https://doi.org/10.1016/S0022-2275(20)38426-1.

    Article  CAS  PubMed  Google Scholar 

  95. Tamadon-Nejad, S., Ouliass, B., Rochford, J., and Ferland, G. (2018) Vitamin K deficiency induced by warfarin is associated with cognitive and behavioral perturbations, and alterations in brain sphingolipids in rats, Front. Aging Neurosci., 10, 213, https://doi.org/10.3389/fnagi.2018.00213.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Carrié, I., Portoukalian, J., Vicaretti, R., Rochford, J., Potvin, S., and Ferland, G. (2004) Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain, J. Nutr., 134, 167-172, https://doi.org/10.1093/jn/134.1.167.

    Article  PubMed  Google Scholar 

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Funding

The work was supported by the Program of Development of the Lomonosov Moscow State University, project no. 23-SCH04-34.

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Conceptualization, analysis of literature – A.I.D. and L.N.N.; writing an original draft – A.I.D., O.I.K., and L.N.N.; visualization – A.I.D., writing review and editing – A.I.D., I.A.R., O.I.K., and L.N.N., acquiring funding – I.A.R., T.N.K., and L.N.N.; supervision – L.N.N. All authors have read and edited the paper.

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Correspondence to Lidia N. Nefedova.

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Translated from Uspekhi Biologicheskoi Khimii, 2024, Vol. 64, pp. 117-142.

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Diachenko, A.I., Rodin, I.A., Krasnova, T.N. et al. The Role of Vitamin K in the Development of Neurodegenerative Diseases. Biochemistry Moscow 89 (Suppl 1), S57–S70 (2024). https://doi.org/10.1134/S0006297924140049

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