A new therapeutic approach for neurodegenerative diseases.
Nowadays, neurodegenerative diseases are a very serious problem. Scientists are trying to discover all the mechanisms for the formation of diseases such as Alzheimer’s, as well as finding a way to diagnose them faster and treat them more effectively. An interesting fact is that a research group led by professor Emoto has conducted a series of animal studies, the result of which was the discovery of a potential therapeutic approach for neurodegenerative diseases. The details of those experiments were shown in the article “Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging”.
The authors’ purpose was to determine the influence of gluthathione (GSH) on the redox state in the mouse brain. In order to measure the GSH level in animal models, electron paramagnetic resonance (EPR) imaging and a redox-sensitive nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramrthylpiperidine-1-oxyl (MCP), were used.
As emphasized, the antioxidants defence system, endogenous antioxidants compounds and enzymatic systems are able to protect the brain from oxidative damage. On the one hand, GSH and ascorbic acid (AsA) are the main endogenous antioxidants. More importantly, their level of concentration could change in the case of a disease. It should be mentioned that AsA, in contrast to GSH, directly influences the reduction of nitroxides. On the other hand, nitroxide probes, once introduced into the animal’s body, are easily reduced under the oxidative stress condition. The reduction rate of nitroxides may be considered as a ratio of in vivo redox state. Therefore, the capabilities of EPR imaging and the MCP probe have been used in this examination. On the basis of the map of MCP reduction rate, a visualization of the redox state in an animal model under oxidative stress has been made.
Due to the reduction of GSH levels in the animal’s body, the redox map of mice brain (control and GSK-depleted) has shown a significant change in the redox state. The linear relationship between the reduction rate of nitroxide probe and the GSH concentration in both control and GSH-depleted mice, has been observed. Therefore, this correlation could be used as a potential method for estimating the GSK levels in vivo from the redox map. Of course, this type of measurement could be conducted with the use of EPR and a nitroxide probe.
It is important to emphasize that GSH levels decrease in the case of diseases related to oxidative stress, such as Alzheimer’s disease. The increase of GSK levels has a potential approach for creating therapies against neurodegenerative disorders. The contribution of GSK to neurodegenerative diseases needs detailed studies, and fortunately EPR imaging could be helpful in such research.
Emoto MC, Matsuoka Y, Yamada KI, Sato-Akaba H, Fujii HG; Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging; Biochem Biophys Res Commun. 2017 Apr 15;485(4):802-806; DOI: 10.1016/j.bbrc.2017.02.134.