Glutathione in multiple sclerosis: More than just an antioxidant?

Abstract

Abstract:Oxidative stress has been strongly implicated in both the inflammatory and neurodegenerative pathological mechanisms in multiple sclerosis (MS). In response to oxidative stress, cells increase and activate their cellular antioxidant mechanisms. Glutathione (GSH) is the major antioxidant in the brain, and as such plays a pivotal role in the detoxification of reactive oxidants. Previous research has shown that GSH homeostasis is altered in MS. In this review, we provide a comprehensive overview on GSH metabolism in brain cells, with a focus on its involvement in MS. The potential of GSH as an in vivo biomarker in MS is discussed, along with a short overview of improvements in imaging methods that allow non-invasive quantification of GSH in the brain. These methods might be instrumental in providing realtime measures of GSH, allowing the assessment of the oxidative state in MS patients and the monitoring of disease progression. Finally, the therapeutic potential of GSH in MS is discussed.

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

“…Each method identified sets of metabolites related to impaired redox homeostasis and glutathione metabolism (e.g., changes in γ-glutamyl amino acids) (14). These findings are consistent with a large body of literature implicating a role of oxidative stress in MS (15,16).…”

Glutathione-Dependent Detoxification Processes in Astrocytes

“…Due to the dependence of many cellular processes on GSH it is not surprising that an impaired GSH metabolism has been connected with human diseases [3][4][5][6]. This appears to be especially the case for neurological disorders as ample evidence connects disturbances in the GSH metabolism of the brain with the progression of neurological disorders [7,8], including Parkinson's disease [9], Alzheimer's disease [10], multiple sclerosis [11] as well as schizophrenia and bipolar disorder [12]. Also alterations of cognitive functions with ageing have been correlated with a decline in GSH content in brain and with impaired GSH-dependent functions [13].…”

Glutathione transferases and neurodegenerative diseases

“…class Alpha GST) should be mentioned (Hurst et al, 1998) and in general the antioxidant function of GSTs in the removal of short-lived lipid hydroperoxides that break down to yield (Saharan and Mandal, 2014). This picture emphasizes the concept that GSH homeostasis and its cellular functions are mediated by a number of different enzymes involved in the ADDS (Carvalho et al, 2014;Satoh et al, 2014). A. Cys 1-Peroxiredoxin (Cys 1-Prx) removes peroxides by the aid of GSH/GST system (Manevich et al, 2003).…”