Exploring the Link Between Glucose Metabolism and Multiple Sclerosis Progression

Multiple sclerosis (MS) is a complex and debilitating disease of the central nervous system (CNS) that is perceived to result from the autoimmune effect of T cells damaging the myelin sheath. However, the exact pathogenesis of the disease remains elusive. Recent studies have shed light on the role of disturbed glucose metabolism in MS, which may provide new perspectives for understanding the disease mechanism and potentially leading to new treatments.

In the 1950s, initial studies described the possibility of defective pyruvate metabolism in MS patients. These studies observed elevated blood pyruvate levels in both fasting and postprandial times in patients with relapse. Similar findings were reported by other investigators, hinting at a possible abnormality of pyruvate metabolism in MS patients. The connection between disturbed pyruvate metabolism and MS progression was further strengthened by the observation of increased levels of Krebs cycle acids like alpha-ketoglutarate in fasting and citrate after glucose intake in MS patients [1].

Glucose Metabolism in MS
Under normal circumstances, complex molecules are metabolized into simpler molecules through their respective pathways. In the CNS, differential expression of genes encoding enzymes of the glucose metabolic pathway may result in neurological deficits. Studies have shown that there is a possible role of impaired energy metabolism in the CNS of MS patients. Elevated levels of pyruvate and α-ketoglutarate have been found in MS patients, indicating a disturbance in glucose metabolism [1,3].

Mitochondrial Defects
Mitochondrial defects have been implicated in MS, as oxidative stress-induced mitochondrial dysfunction likely alters glucose metabolism and impairs neuronal function. Demyelinated axons in MS lesions have an increased energy demand, which may be met by altered glucose metabolism. The OxPhos system, the last step in glucose metabolism, is critical for maintaining a proton gradient and producing ATP. MS patients have elevated levels of essential glucose metabolites in the cerebrospinal fluid (CSF), serum, and brain compared to non-neurological controls [4].

Implications for Understanding MS
These observations open new perspectives for understanding the metabolic dynamics in MS. However, many puzzling aspects and critical questions need to be addressed. Much more research is required to fully unravel the disease mechanism, and a proper understanding of the disease could eventually lead to new treatments. The connection between glucose metabolism and MS progression highlights the importance of exploring the role of disturbed glucose metabolism in pathophysiological brain function [2].

Conclusion
In conclusion, the studies on perturbed glucose metabolism in MS provide valuable insights into the disease pathogenesis. The findings suggest that altered glucose metabolism may play a crucial role in MS progression, and further research is needed to fully understand the mechanisms involved. This knowledge could potentially lead to the development of new treatments for MS, which currently lacks a cure.

References
1. Mathur, D., López-Rodas, G., Casanova, B., & Marti, M. B. (2014). Perturbed glucose metabolism: insights into multiple sclerosis pathogenesis. Frontiers in Neurology, 5, 250.
2. Maric, G., Lalic, K., Pekmezovic, T., Tamas, O., Rajkovic, N., Rasulic, I., ... & Drulovic, J. (2020). Could the performance of oral glucose tolerance test contribute to the brain health-focused care in multiple sclerosis?. Multiple Sclerosis and Related Disorders, 46, 102536.
3. Nijland, P. G., Molenaar, R. J., van der Pol, S. M., van der Valk, P., van Noorden, C. J., de Vries, H. E., & van Horssen, J. (2015). Differential expression of glucose-metabolizing enzymes in multiple sclerosis lesions. Acta neuropathologica communications, 3, 1-13.
4. Mathur, D., María-Lafuente, E., Ureña-Peralta, J. R., Sorribes, L., Hernández, A., Casanova, B., ... & Burgal-Marti, M. (2017). Disturbed glucose metabolism in rat neurons exposed to cerebrospinal fluid obtained from multiple sclerosis subjects. Brain sciences, 8(1), 1.