Monitoring the Redox Status in Multiple Sclerosis

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.

Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer’s Disease in Rats

“…Further, the brain has greater metabolic activity, high content of polyunsaturated fatty acids, less glutathione and high oxygen consumption, making it explicitly available to free radical attack [36,37]. Imbalance between the production of reactive oxidizing metabolites and their elimination by the enzymatic or non-enzymatic antioxidant system causes the state of oxidative stress [38]. An excess of free radicals causes damage to the membrane's lipids and proteins, which eventually leads to a decrease in GSH and an increase in MDA levels in the brain [34].…”

Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid

“…In MS, oxidative stress, and the excess of ROS or RONS are among the contributors to neuronal- and axonal injury [ 208 , 209 , 210 ]. Animal model studies showed LA treatment decreased matrix metalloproteinase (MMP), IFN-γ, and interleukin-4 (IL-4) [ 211 ] and the reduced expression of soluble cell adhesion molecule (ICAM) in spinal cord tissue [ 212 ].…”

Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

“…Oxidative stress condition is characterized by the imbalance between the production of free radicals and their counteraction by antioxidant defenses [ 42 ]. An increasing number of studies has shown that OS plays an important role in the pathogenesis of MS [ 5 , 6 , 22 , 23 , 43 , 44 ]. OS, associated with inflammation and neuronal damage, results in the oxidation of cellular components, such as proteins, lipids, and nucleic acids potentiates leading to a vicious cycle that can accelerate the progression of the disease [ 5 , 44 , 45 , 46 , 47 ].…”

“…An increasing number of studies has shown that OS plays an important role in the pathogenesis of MS [ 5 , 6 , 22 , 23 , 43 , 44 ]. OS, associated with inflammation and neuronal damage, results in the oxidation of cellular components, such as proteins, lipids, and nucleic acids potentiates leading to a vicious cycle that can accelerate the progression of the disease [ 5 , 44 , 45 , 46 , 47 ]. OS is involved in several characteristic process of MS such as the activation of immune cells, especially T cells [ 15 ], the loss of BBB selectivity [ 48 ], promotion of T-cell migration and infiltration into the CNS [ 49 ] and the increased expression of the cytokine network [ 50 ] ( Figure 2 ).…”

“…The majority of untreated RR-MS patients do eventually progress into secondary progressive (SP-MS) course caractherized by a history of a gradual disability progression, independent of relapses; primary progressive (PP-MS) course, characterized by worsening of neurological functions from the onset of the disease [ 3 ]. As few as 5% of MS patients present progressive neurological deficits with acute attacks with or without recovery, named progressive-relapsing MS (PR-MS) [ 4 , 5 ]. In 2013, these originally established MS subtypes were revised to review potential imaging and biological correlates and to reflect further MS clinical aspects.…”