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Hypothalamic-mediated model for Creutzfeldt-Jakob disease: relation to hemispheric chemical dominance
Rave Kumar Kurup1, Parameswara Achutha Kurup
1Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India.
Insights
Creutzfeldt-Jakob Disease (CJD) shows an upregulated isoprenoid pathway and increased digoxin synthesis, particularly with right hemispheric dominance. These metabolic changes in CJD patients highlight the pathway's role in disease pathogenesis.
Area of Science:
- Biochemistry
- Neuroscience
- Metabolic pathways
Background:
- The isoprenoid pathway is crucial for cellular functions.
- Alterations in this pathway are implicated in various neurological disorders.
- Creutzfeldt-Jakob Disease (CJD) is a fatal neurodegenerative prion disease.
Purpose of the Study:
- To investigate the isoprenoid pathway, including endogenous digoxin synthesis, in Creutzfeldt-Jakob Disease (CJD).
- To compare these metabolic changes with those in patients exhibiting right or left hemispheric chemical dominance.
Main Methods:
- Assessment of the isoprenoid pathway and digoxin levels in CJD patients.
- Comparative analysis in patients with diagnosed right and left hemispheric dominance.
- Evaluation of tryptophan and tyrosine catabolites, dolichols, glycoconjugates, lysosomal stability, ubiquinone, free radicals, and membrane lipid composition.
Main Results:
- Upregulated isoprenoid pathway and increased digoxin synthesis observed in CJD patients and those with right hemispheric dominance.
- Patients with right hemispheric dominance showed increased tryptophan catabolites, elevated dolichol and glycoconjugate levels, reduced lysosomal stability, low ubiquinone, increased free radicals, and altered membrane lipid ratios.
- Left hemispheric dominance presented with reversed metabolic patterns.
Conclusions:
- The isoprenoid pathway is significantly altered in CJD, correlating with right hemispheric chemical dominance.
- These findings suggest a potential role for the isoprenoid pathway in CJD pathogenesis.
- Hemispheric chemical dominance may influence metabolic dysregulation in neurodegenerative conditions.
Abstract:
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.