The Glutathione System: A New Drug Target in Neuroimmune Disorders

By G. Morris et al.

Abstract

Glutathione (GSH) has a crucial role in cellular signaling and antioxidant defenses either by reacting directly with reactive oxygen or nitrogen species or by acting as an essential cofactor for GSH S-transferases and glutathione peroxidases.

GSH acting in concert with its dependent enzymes, known as the glutathione system, is responsible for the detoxification of reactive oxygen and nitrogen species (ROS/RNS) and electrophiles produced by xenobiotics. Adequate levels of GSH are essential for the optimal functioning of the immune system in general and T cell activation and differentiation in particular. GSH is a ubiquitous regulator of the cell cycle per se. GSH also has crucial functions in the brain as an antioxidant, neuromodulator, neurotransmitter, and enabler of neuron survival.

Depletion of GSH leads to exacerbation of damage by oxidative and nitrosative stress; hypernitrosylation; increased levels of proinflammatory mediators and inflammatory potential; dysfunctions of intracellular signaling networks, e.g., p53, nuclear factor-?B, and Janus kinases; decreased cell proliferation and DNA synthesis; inactivation of complex I of the electron transport chain; activation of cytochrome c and the apoptotic machinery; blockade of the methionine cycle; and compromised epigenetic regulation of gene expression.

As such, GSH depletion has marked consequences for the homeostatic control of the immune system, oxidative and nitrosative stress (O&NS) pathways, regulation of energy production, and mitochondrial survival as well. GSH depletion and concomitant increase in O&NS and mitochondrial dysfunctions play a role in the pathophysiology of diverse neuroimmune disorders, including depression, myalgic encephalomyelitis/chronic fatigue syndrome and Parkinson’s disease, suggesting that depleted GSH is an integral part of these diseases.

Therapeutical interventions that aim to increase GSH concentrations in vivo include N-acetyl cysteine; Nrf-2 activation via hyperbaric oxygen therapy; dimethyl fumarate; phytochemicals, including curcumin, resveratrol, and cinnamon; and folate supplementation.

Source: Morris G, Anderson G, Dean O, Berk M, Galecki P, Martin-Subero M, Maes M. Mol Neurobiol. 2014 Apr 22. [Epub ahead of print]

1 Star2 Stars3 Stars4 Stars5 Stars (16 votes, average: 4.55 out of 5)
Loading...



3 thoughts on “The Glutathione System: A New Drug Target in Neuroimmune Disorders”

  1. IanH says:

    The sublingual GSH does work. In fact you can take any powdered version of GSH under the tongue for about 1 minute and blood levels rise significantly.

  2. richcarson says:

    Liposomal glutathione is also very effective in raising levels of the glutathione enzymes in the body, and in fact, ProHealth sells just such a product. http://ow.ly/wjK3E

  3. GlutathionePRO says:

    You can orally supplement GSH levels with the bioavailable form, Acetyl Glutathione.
    Regular glutathione supplements have also been proven to increase levels when taken in high doses long term. However much of the supplement goes to waste due to damage caused in the digestive tract. For the best results use an Acetyl glutathione supplement paired with GSH precursors like N Acetylcysteine, R-alpha lipoic acid and Silymarin.

Leave a Reply