Abstract

Glutathione (GSH) is an important antioxidant implicated in several physiological functions, including the oxidation−reduction reaction balance and brain antioxidant defense against endogenous and exogenous toxic agents. Altered brain GSH levels may reflect inflammatory processes associated with several neurologic disorders. An accurate and reliable estimation of cerebral GSH concentrations could give a clear and thorough understanding of its metabolism within the brain, thus providing a valuable benchmark for clinical applications. In this context, we aimed to provide an overview of the different magnetic resonance spectroscopy (MRS) technologies introduced for in vivo human brain GSH quantification both in healthy control (HC) volunteers and in subjects affected by different neurological disorders (e.g., brain tumors, and psychiatric and degenerative disorders). Additionally, we aimed to provide an exhaustive list of normal GSH concentrations within different brain areas. The definition of standard reference values for different brain areas could lead to a better interpretation of the altered GSH levels recorded in subjects with neurological disorders, with insights into the possible role of GSH as a biomarker and therapeutic target.

Highlights

  • Glutathione (GSH) is an antioxidant metabolite originating from glutamic acid (Glu), cysteine (Cys), and Glycine (Gly) amino acids, globally present in all mammalian cells [1].Among its many roles, GSH is mainly implicated in oxidation−reduction reactions, acting as a protector against endogenous and exogenous toxic agents like reactive oxygen species (ROS) and reactive nitrogen species (RNS) [2]

  • As high levels of ROS may lead to cerebral tissue damage, the altered GSH concentration of specific brain areas has been described in several neurologic disorders, including epilepsy [6,7], multiple sclerosis [8,9], Alzheimer’s disease [10], Parkinson’s disease [11,12], and psychiatric disorders [13,14,15,16]

  • The methods reported in the literature are highly heterogeneous, we provide a detailed description of the current methods for GSH measurement within the sections, differentiating unedited and edited spectrum techniques

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Summary

Introduction

Glutathione (GSH) is an antioxidant metabolite originating from glutamic acid (Glu), cysteine (Cys), and Glycine (Gly) amino acids, globally present in all mammalian cells [1].Among its many roles, GSH is mainly implicated in oxidation−reduction reactions, acting as a protector against endogenous and exogenous toxic agents like reactive oxygen species (ROS) and reactive nitrogen species (RNS) [2]. Glutathione (GSH) is an antioxidant metabolite originating from glutamic acid (Glu), cysteine (Cys), and Glycine (Gly) amino acids, globally present in all mammalian cells [1]. As high levels of ROS may lead to cerebral tissue damage, the altered GSH concentration of specific brain areas has been described in several neurologic disorders, including epilepsy [6,7], multiple sclerosis [8,9], Alzheimer’s disease [10], Parkinson’s disease [11,12], and psychiatric disorders [13,14,15,16]. In order to provide a clear and thorough understating of GSH metabolism within the brain, an accurate and reliable estimation of cerebral concentrations needs to be performed. GSH biosynthesis and metabolism were tested in vitro, Antioxidants 2021, 10, 1407.

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