Hypothalamic-mediated model for Creutzfeldt-Jakob disease: relation to hemispheric chemical dominance.
The isoprenoid pathway including endogenous digoxin was assessed in Creutzfeldt-Jakob Disease (CJD). 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 CJD and in those with right hemispheric chemical dominance. In this group of patients (i) the tryptophan catabolites were increased and the tyrosine catabolites reduced, (ii) the dolichol and glycoconjugate levels were elevated, (iii) lysosomal stability was reduced, (iv) ubiquinone levels were low and free radical levels increased, and (v) the membrane cholesterol:phospholipid ratios were increased and membrane glyco conjugates reduced. On the other hand, in patients with left hemispheric chemical dominance, the reverse patterns were obtained. The role of the isoprenoid pathway in the pathogenesis of CJD and its relation to hemispheric chemical dominance is discussed.
Kurup
Rave Kumar
RK
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India.
Kurup
Parameswara Achutha
PA
D001923:Brain Chemistry / Q000502:physiology; D007562:Creutzfeldt-Jakob Syndrome / Q000503:physiopathology*; D004077:Digoxin / Q000097:blood*; D004286:Dolichols / Q000097:blood; D004292:Dominance, Cerebral / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000097:blood; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005609:Free Radicals / Q000097:blood; D006023:Glycoproteins / Q000097:blood; D006025:Glycosaminoglycans / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008247:Lysosomes / Q000378:metabolism; D008274:Magnesium / Q000097:blood; D016555:Matched-Pair Analysis; D008954:Models, Biological; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D004791:Enzyme Inhibitors; D005609:Free Radicals; D006023:Glycoproteins; D006025:Glycosaminoglycans; D018377:Neurotransmitter Agents; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; D014443:Tyrosine; D004077:Digoxin; D014364:Tryptophan; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium