Hypothalamic digoxin, hemispheric dominance, and neuroimmune integration.
The isoprenoid pathway produces three key metabolites--digoxin (membrane Na(+)-K+ ATPase inhibitor, regulator of neurotransmitter transport, and immunomodulatory agent), dolichol (regulatory of N-glycosylation of proteins), and ubiquinone (free-radical scavenger). The pathway was assessed in systemic lupus erythematosis with neuropsychiatric manifestations, slow viral diseases (subacute sclerosing panencephalitis [SSPE], and Creutzfeldt-Jakob disease [CJD]) and patients with recurrent respiratory infections. This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with neurolupus, SSPE, and CJD, and in those with right hemispheric dominance. The tryptophan catabolites were increased and the tyrosine catabolites reduced. In these patients the dolichol and glycoconjugate levels were elevated and lysosomal stability was reduced. The ubiquinone levels were low and free-radical levels increased in these patients. The membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with recurrent respiratory infection and left hemispheric dominance, the reverse patterns and hypodigoxinemia with a downregulated isoprenoid pathway were noticed. The isoprenoid pathway is important in the pathogenesis of neurolupus, CJD, SSPE, and recurrent respiratory infections. Hypothalamic digoxin and chemical hemispheric dominance play an important role in the regulation of immunity.
D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000503:physiopathology; D004077:Digoxin / Q000378:metabolism*; D004286:Dolichols / Q000097:blood; D004910:Erythrocyte Membrane / Q000201:enzymology; D007839:Functional Laterality; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D001523:Mental Disorders / Q000209:etiology; D015213:Neuroimmunomodulation; D012008:Recurrence; D012140:Respiratory Tract Diseases / Q000378:metabolism / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood; D013344:Subacute Sclerosing Panencephalitis / Q000378:metabolism / Q000503:physiopathology; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D006025:Glycosaminoglycans; D014451:Ubiquinone; D014443:Tyrosine; D004077:Digoxin; D014364:Tryptophan; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase