Abstract
Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life.
Highlights
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the brain and spinal cord, which over 2.2 million people worldwide suffer from; it affects primarily young adults from 20 to 40 years of age
Redox biomarkers are classified by original cellular components and enzyme mechanisms of action in redox homeostasis
Redox status can be assessed by the measurement of reactive chemical species, oxidative or antioxidative enzyme activity, and degradation products derived from proteins, amino acids, lipid membrane, and nucleic acids
Summary
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the brain and spinal cord, which over 2.2 million people worldwide suffer from; it affects primarily young adults from 20 to 40 years of age. Almost 90% of RRMS patients progress to steady neurological decline within 25 years, termed secondary progressive MS (SPMS). 10% of MS patients suffer from steady deterioration of neurological functions without recovery, termed primary progressive MS (PPMS). As few as 5% of MS patients present progressive neurological deficits with acute attacks with or without recovery, termed progressive-relapsing MS (PRMS) [17]. CSF samples of patients in the remission stage of RRMS showed higher purine oxidation product uric acid, reduced antioxidant, and increased intrathecal synthesis of IgG [31]. Monitoring different redox components, including oxidative enzymes, antioxidative enzymes, and degradation products during the disease progression helps to evaluate the redox status of MS patients, expediting the building of the most appropriate personalized treatment plans for MS patients [33]
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