Vitamin K-dependent proteins in the developing and aging nervous system

Although the warfarin embryopathy syndrome, with its neurologic and bone abnormalities, has been known for decades, the role of vitamin K in the brain has not been studied systematically. Recently, it was demonstrated that vitamin K-dependent carboxylase expression is temporally regulated in a tissue-specific manner with high expression in the nervous system during the early embryonic stages and with liver expression after birth and in adult animals. This finding, along with the discovery of wide distribution of the novel vitamin K-dependent growth factor, Gas6, in the central nervous system, provides compelling evidence of a biologic role of vitamin K during the development of the nervous system. In animals and bacteria, vitamin K was observed to influence the brain sulfatide concentration and the activity and synthesis of an important enzyme involved in brain sphingolipids biosynthesis. Taken together, previous research results point to a possible role of vitamin K in the nervous system, especially during its development. Hence, the knowledge of the biologic role of vitamin K in the brain may be important for unveiling the mechanisms of normal and pathologic development and aging of the nervous system. The role of the vitamin K-dependent protein Gas6 in activation of signal transduction events in the brain in light of the age-related changes in the nervous system is also discussed.