Background: Although there are many hypotheses of multiple sclerosis' (MS') origin, it remains a disease of unknown and diverse etiologies: MS appears to be a multi-system disease.
Objectives: We here examine in details a psycho-thermogenic hypothesis of MS origin aimed to explane how CNS could modulate cross-talk between (i) stress-induced adrenergic signaling via five types of adrenergic receptors and (ii) mitochondrial energy production via three isoforms of mitochondrial uncoupling proteins (UCP).
Methods: We applied a basic Systems Biology approach to analyze diversification of signaling and metabolomic pathways.
Results: We made a map including all these processes. This map highlights a regulation of mitochondrial metabolism via adrenergic signaling. Inclusion of positive and negative feed-backs enables some comprehension of the complexity of the signal transduction. The thrust of the signaling results in both an induction of UCP expression and a production of UCP activators, i.e. free fatty acids. Depending on the isotypes involved, the UCPs then uncouple the respiratory chain from ATP synthesis, thereby accelerating respiration, dissipating the extra Gibbs energy, and releasing much heat. This suggests that deregulated chemical, thermodynamic, temporal and spatial control of individual isoforms of the adrenergic receptors and UCPs, may contribute to initiation and progression of some cases of MS. A defective serotoninergic regulation of the interaction between adrenergic signaling in CNS is considered and appears critical for the MS pathology progression and recovery.
Conclusion: In adipose tissue, deregulated cross-talk may result in local overheating with subsequent burn-like injury of neighboring neurons, blood vessels and tissues. In neurons the concomitant decrease of ATP production may lead to insufficient neuronal signaling due to suppression of action potential support as well as neurotransmitter release, reuptake, and regeneration. This should then result in the neuronal symptoms of MS. These findings may pave new MS research avenues, with new ways of diagnostics, prevention and therapy of some cases of MS.