title: 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.
authors.affiliation: Department of Functional Biology, University of Valencia , Valencia , Spain.
authors.forename: Deepali
authors.initials: D
authors.lastname: Mathur
authors.affiliation: Department of Biochemistry and Molecular Biology, INCLIVA Biomedical Research Institute, University of Valencia , Valencia , Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: López-Rodas
authors.affiliation: Hospital Universitari i Politècnic La Fe , València , Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Casanova
authors.affiliation: Multiple Sclerosis Laboratory, Department of Biomedicine, Prince Felipe Research Center , Valencia , Spain.
authors.forename: Maria Burgal
authors.initials: MB
authors.lastname: Marti
keywords: brain glucose metabolism; cell-specific mechanisms; mitochondrial defects; multiple sclerosis; neurodegenerative diseases