Therapeutic potential of glutathione-enhancers in stress-related psychopathologies. (July 2020)

• Record Type: Journal Article
• Authors: Zalachoras, Ioannis; Hollis, Fiona; Ramos-Fernández, Eva; Trovo, Laura; Sonnay, Sarah; Geiser, Eveline; Preitner, Nicolas; Steiner, Pascal; Sandi, Carmen; Morató, Laia
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 114(2020)
• Page Start: 134
• Page End: 155
• Publication Date: 2020-07
• Subjects: Psychogenic stress -- Brain -- Oxidative stress -- Glutathione (GSH) -- Nuclear factor erythroid-2-related factor 2 (Nrf2) -- Depression -- Anxiety -- N-acetyl-cysteine -- Glycine -- Taurine -- Whey proteins -- Glutamine -- Sulforaphane -- Dimethyl fumarate -- Curcumin -- Melatonin -- Trehalose -- Ergothioneine -- l-carnitine -- Puerarin; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2020.03.015
• Languages: English
• ISSNs: 0149-7634

Abstract

Graphical abstract: Highlights: Mitochondria meet the high energetic demand of the brain during psychogenic stress. Chronic stress leads to oxidative stress and lower glutathione (GSH) levels. Depression and anxiety are associated with decreased levels of GSH. The nuclear factor erythroid-2-related factor 2 (Nrf2) regulates GSH synthesis. GSH precursors and Nrf2 activators prevent stress-induced behavioral alterations. Abstract: The mammalian brain has high energy demands, which may become higher in response to environmental challenges such as psychogenic stress exposure. Therefore, efficient neutralization of reactive oxygen species that are produced as a by-product of ATP synthesis is crucial for preventing oxidative damage and ensuring normal energy supply and brain function. Glutathione (GSH) is arguably the most important endogenous antioxidant in the brain. In recent years, aberrant GSH levels have been implicated in different psychiatric disorders, including stress-related psychopathologies. In this review, we examine the available data supporting a role for GSH levels and antioxidant function in the brain in relation to anxiety and stress-related psychopathologies. Additionally, we identify several promising compounds that could raise GSH levels in the brain by either increasing the availability of its precursors or the expression of GSH-regulating enzymes through activation of Nuclear factor erythroid-2-related factor 2 (Nrf2). Given the high tolerability and safety profile of these compounds, they may represent attractive new opportunities to complement existing therapeutic manipulations against stress-related psychopathologies.