Perturbed Glucose Metabolism: Insights into Multiple Sclerosis Pathogenesis

Abstract

Multiple sclerosis (MS) is a complex debilitating disease of the central nervous system (CNS) perceived to result from the autoimmune effect of T cells in damaging myelin sheath. However, the exact pathogenesis of the disease remains elusive. Initial studies describing the possibility of defective pyruvate metabolism in MS were performed in 1950s. The group observed elevated blood pyruvate level in both fasting and postprandial times in MS patients with relapse. Similarly, other investigators also reported increased fasting pyruvate level in this disease. These reports hint to a possible abnormality of pyruvate metabolism in MS patients. In addition, increase in levels of Krebs cycle acids like alpha-ketoglutarate in fasting and citrate after glucose intake in MS patients further strengthened the connection of disturbed pyruvate metabolism with MS progression. These studies led the investigators to explore the role of disturbed glucose metabolism in pathophysiological brain function. Under normal circumstances, complex molecules are metabolized into simpler molecules through their respective pathways. Differential expression of genes encoding enzymes of the glucose metabolic pathway in CNS may result in neurological deficits. In this review article, we discuss the studies related to disturbed carbohydrate metabolism in MS and other neurodegenerative diseases. These observations open new perspectives for the understanding of metabolic dynamics in MS yet 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.

Integration of metabolomics and proteomics in multiple sclerosis: From biomarkers discovery to personalized medicine

“…As it has been reported by Reinke et al. after H‐NMR spectroscopy analysis, eight different significantly metabolites were found between MuS and non‐MuS CSF specimens. Citrate, 3‐hydroxybutyrate, Phenylalanine, 2‐hydroxyisovalerate, and mannose were significantly diminished in MuS patients, as shown in Table .…”

A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica

“…Interestingly, the brain also uses ketone bodies as an alternative energy source. 27 Thus, alteration in glycolysis and the synthesis and degradation of ketone bodies is consistent with an alteration in energy generation. Besides energy generation, ketone bodies are also associated with fatty acid metabolism.…”

Nontarget metabolomics profiling of neuromyelitis optica spectrum disorder

“…Teklab Gebregiworgis investigated glycolysis and ketone body synthesis and decomposition as vital metabolic pathways in NMOSD and multiple sclerosis (Gebregiworgis et al, ). Other research has shown that the brain comsumes a quarter of the whole body's glucose supply to sustain brain functioning, and when the blood gludcose supply fails to meet brain energy needs, the ketone body can alternatively serve as an energy source (Mathur, Lopez‐Rodas, Casanova, & Marti, ). In the experimental group, we observed the reduction of plasma tyrosine content and the elevation of phenylalanine.…”