Glutathione in multiple sclerosis

Abstract

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterised mainly as an autoimmune neurodegenerative disorder. Its cause is unknown but multifactorial; however, some studies suggest that oxidative stress may be one of the sources, or a consequence of the disease, from loss of oxidant/antioxidant balance. This review studies glutathione, one of the most important agents of the endogenous antioxidant defence system, protecting cells from damage caused by oxidative stress. It evaluates glutathione and the enzymes glutathione peroxidase and glutathione reductase in various forms and stages of the disease. Analysis of a literature search suggests that the scientific community is not unanimous in its views, so more studies are required of patients with different forms of the disease and its manifestations, taking into account that the body functions as a whole and reacts in a compensatory manner. It would seem imperative to achieve a consensus on the pathogenesis responsible for severe disability, and explore sensitive biomarkers of its progression and indicators of oxidative stress. It is also important to promote the development of new therapies, with more studies on other substances such as acrolein, lipoic acid and dimethyl fumarate. Clarification of the mechanisms involved in oxidative stress, in different forms of multiple sclerosis, could result in improvements in the monitoring and prognosis of the disease, with subsequent increases in a patient's quality of life.

Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells

“…Decreased levels of Grx-3 render cells susceptible to cellular oxidative stress (Zhang et al, 2017), whereas overexpression of nuclear-targeted Grx-3 is sufficient to suppress cells' sensitivity to oxidant treatments and reduce reactive oxygen species production (Kenchappa et al, 2004; Pham et al, 2015). Mitochondrial dysfunction, in addition to excessive oxidative stress, plays a significant role in an array of neurodegenerative diseases (Chen, 2011; Cozzolino and Carrì, 2012; Federico et al, 2012; Ferreira et al, 2013; Smeyne and Smeyne, 2013; Yan et al, 2013; Camilleri and Vassallo, 2014; Saharan and Mandal, 2014; Wang et al, 2014; Gu et al, 2015). Grx, likewise, helps maintain mitochondrial integrity by preventing the loss of mitochondrial membrane potential (MMP) caused by oxidative insult (Saeed et al, 2008).…”

Glutathione redox imbalance in brain disorders

“…], bipolar disorder [9], schizophrenia [10], amyotrophic lateral sclerosis [11], Huntington's disease [12], and multiple sclerosis [13] (Table 1). GSH deficit may precede the neuropathology of these diseases, and neuronal GSH depletion may be a primary cause of these brain diseases.…”

Multiple Sclerosis and Its Relationship with Oxidative Stress, Glutathione Redox System, ATPase System, and Membrane Fluidity

“…Glutamate in turn causes neurodegeneration through the AMPA and NMDA receptors in oligodendrocytes and astrocytes (Figure 3). It is possible to explain the role of mediators using an experimental model of autoimmune encephalitis: Protection against the experimental disease occurs after administration of a glutamate antagonist [10].…”

“…Glutathione has been reported to protect mitochondrial complex I activity against nitrosative stress, as S-nitrosoglutathione is formed. When this complex increases its content of nitrotyrosine and nitrosothiol groups in response to nitrosative stress, its activity is inhibited and therefore ATP production is diminished, which causes neuronal degeneration [10]. The role of glial cells in generating ROS in MS and the selective vulnerability of neurons is due to activated glial cells surrounding these neurons, as these glial cells are also directly involved in GSH levels.…”