Abstract
This study assessed the isoprenoid pathway‐related biochemical cascade in multiple sclerosis, and in this work we discuss the pivotal role of hypothalamic digoxin and membrane sodium‐potassium ATPase inhibition in the pathogenesis of multiple sclerosis. Our results showed that there was an elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol levels and a reduction in red blood cell (RBC) membrane sodium potassium ATPase activity, serum ubiquinone, and magnesium levels. Serum tryptophan, serotonin, strychnine, nicotine, and quinolinic acid were elevated whereas tyrosine, dopamine, morphine, and noradrenaline were decreased. The total serum glycosaminoglycans, hyaluronic acid, heparin, and heparan sulphate were elevated and levels of chondroitin sulphates and dermatan sulphate were reduced in multiple sclerosis. The serum glycolipids as well as the hexose, fucose, and sialic acid carbohydrate residues of serum glycoproteins were elevated. The activity of glycosaminoglycan degrading enzymes was elevated. The activity of glycohydrolases—beta galactosidase and beta fucosidase—were increased and beta glucosidase reduced in the serum. The RBC membrane glycosaminoglycan, the hexose and fucose carbohydrate residues of glycoproteins, and the cholesterol:phospholipid ratio of the RBC membrane were decreased in multiple sclerosis. Membrane Na^+^‐K^+^ ATPase inhibition‐related increased intracellular calcium can produce immune activation via the calcineurin signal transduction system in T cells. Digoxin‐induced altered glycoconjugate metabolism can change the structural integrity of myelin as well as result in immune dysregulation caused by defective presentation of myelin glycoprotein antigens to CD~8~ cells. Digoxin‐induced defective membrane formation of oligodendrocyte membrane can inhibit remyelination. Digoxin‐related mitochondrial dysfunction can contribute to free radical generation, microglial activation, and oligodendrocyte apoptosis that are important in demyelination. J. Trace Elem. Exp. Med. 15:211–220, 2002. © 2002 Wiley‐Liss, Inc.