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Perturbed glucose metabolism: insights into multiple sclerosis pathogenesis
Deepali Mathur1, Gerardo López-Rodas2, Bonaventura Casanova3
1Department of Functional Biology, University of Valencia , Valencia , Spain.
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.
Insights
Multiple sclerosis (MS) may involve defective pyruvate metabolism, with elevated blood pyruvate and Krebs cycle acids observed in patients. Further research into carbohydrate metabolism could reveal new treatments for this central nervous system disease.
Area of Science:
- Neuroscience
- Metabolic pathways
- Autoimmune diseases
Background:
- Multiple sclerosis (MS) is a debilitating central nervous system (CNS) disease with unclear pathogenesis, though autoimmune T cell activity damaging myelin is suspected.
- Early studies from the 1950s suggested potential defects in pyruvate metabolism in MS patients, noting elevated blood pyruvate levels during relapse.
- Further research indicated increased levels of Krebs cycle intermediates, such as alpha-ketoglutarate and citrate, in MS patients, strengthening the link between disturbed pyruvate metabolism and disease progression.
Purpose of the Study:
- To review existing literature on disturbed carbohydrate metabolism in multiple sclerosis (MS) and other neurodegenerative diseases.
- To explore the potential role of impaired glucose metabolism in the pathophysiology of brain function in MS.
- To highlight new perspectives and critical questions regarding metabolic dynamics in MS.
Main Methods:
- Literature review of studies investigating pyruvate and glucose metabolism in multiple sclerosis (MS).
- Analysis of historical and contemporary research on metabolic abnormalities in the central nervous system (CNS) of MS patients.
- Examination of gene expression patterns related to glucose metabolic pathways in neurological disorders.
Main Results:
- Consistent observations of elevated blood pyruvate levels in MS patients, particularly during relapse.
- Increased levels of Krebs cycle acids (alpha-ketoglutarate, citrate) in MS patients suggest a broader disturbance in carbohydrate metabolism.
- Potential link between altered glucose metabolism and the progression of MS and other neurodegenerative conditions.
Conclusions:
- Disturbed pyruvate and carbohydrate metabolism are implicated in the pathophysiology of multiple sclerosis (MS).
- Understanding these metabolic dynamics offers new avenues for MS research and potential therapeutic strategies.
- Further investigation is crucial to fully elucidate the disease mechanisms and develop effective treatments.
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