Brain energy metabolism and multiple sclerosis: progress and prospects
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Online ISSN 1976-3786 Print ISSN 0253-6269
REVIEW
Brain energy metabolism and multiple sclerosis: progress and prospects Sung Jean Park1 · Ji Woong Choi1
Received: 4 October 2020 / Accepted: 21 October 2020 © The Pharmaceutical Society of Korea 2020
Abstract Multiple sclerosis (MS) is an autoimmune disease accompanied with nerve pain and paralysis. Although various pathogenic causes of MS have been suggested, including genetic and environmental factors, how MS occurs remains unclear. Moreover, MS should be diagnosed based on clinical experiences because of no disease-specific biomarker and currently available treatments for MS just can reduce relapsing frequency or severity with little effects on disease disability. Therefore, more efforts are required to identify pathophysiology of MS and diagnosis markers. Recent evidence indicates another aspect of MS pathogenesis, energy failure in the central nervous system (CNS). For instance, inflammation that is a characteristic MS symptom and occurs frequently in the CNS of MS patients can result into energy failure in mitochondria and cytosol. Indeed, metabolomics studies for MS have reported energy failure in oxidative phosphorylation and alteration of aerobic glycolysis. Therefore, studies on the metabolism in the CNS may provide another insight for understanding complexity of MS and pathogenesis, which would facilitate the discovery of promising strategies for developing therapeutics to treat MS. This review will provide an overview on recent progress of metabolomic studies for MS, with a focus on the fluctuation of energy metabolism in MS.
* Sung Jean Park [email protected] * Ji Woong Choi [email protected] 1
College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, 191 Hambakmoero, Yeonsu‑gu, Incheon 21936, Korea
Keywords Multiple sclerosis · Energy metabolism · Aerobic glycolysis · Metabolomics · Inflammation
Introduction Multiple sclerosis (MS), an autoimmune disorder of the central nervous system (CNS), is one of the most common disease characterized by demyelination of axons, leading to massive immune responses inside of the CNS and neurodegeneration (Vos et al. 2015). More than two million people worldwide suffer from MS (Vos et al. 2015). MS is more likely to develop in relatively younger people of ages between 20 and 40 years, and it rarely develops in children under the age of 10 or seniors over the age of 60. In addition, the occurrence of MS is generally two-fold higher in women than in men. Classically, immunosuppressive agents, including corticosteroids and interferons, have been used to alleviate the symptoms of MS. Recently, new orally available drugs targeting sphingosine 1-phosphate receptors, including fingolimod (GilenyaTM, Novartis, 2010), siponimod (Mayzent®, Novartis, 2019), and ozanimod (ZEPOSIA®, Bristol-Myers Squibb, 2020) were successfully launched. Despite this success, how MS occurs remains unclear, and more efforts are being made to identify promising therapeutic targets. Most studies h
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