Neurodegenerative and inflammatory reactions are related to the antioxidant capacity of cells! If the antioxidant capacity of human cells decreases, which leads to the increase of intracellular oxidative stress, cell aging and withering, it may produce gradually frozen people and colitis and other similar diseases. Academician Li Wenhua of the Genome Research Center of Academia Sinica cooperated with China Medical University and National Taiwan University Hospital, and found that antioxidant enzymes GPx7 and GPx8 can detect and regulate oxidative stress, which can not only balance the redundant oxidative activity of cells, but also assist drug testing and treatment of diseases through inhibitors of related mechanisms.
Lack of GPx7 gene in neurodegenerative diseases can easily lead to atrophy of motor neurons.
Neurons in the brain and spinal cord are particularly sensitive to reactive oxygen species. Dr. Li Wenhua from Academician's Laboratory and Dr. Su from the Institute of Biochemistry of Yangming University found that mice with GPx7 gene deletion will have symptoms of motor neuron degeneration. When they reach the age of 1 1 month (equivalent to middle age), their mobility will be weakened, and about 10% of them will be severely paralyzed. Compared with the average life cycle of normal mice of 2-3 years, the diseased mice with motor neuron degeneration will gradually die 15 months earlier.
The research team further analyzed the spinal cord tissue of sick mice by immunofluorescence staining, and found that the number of motor neurons in sick mice was greatly reduced by about 20% compared with normal mice of the same age, and the synaptic structure of motor neurons connected with muscles gradually shrank and withdrew from the junction, indicating that motor neurons gradually lost their ability to control muscles.
To sum up, the loss of GPx7 will lead to atrophy and apoptosis of motor neurons in the spinal cord, and there will be symptoms similar to gradual freezing such as paralysis of lower limbs; It is also found that the expression of GPx7 in patients with gradual freezing is indeed significantly lower than that in the general population.
GPx8 is the key to treat colitis.
GPx8 can inhibit the inflammatory reaction affected by reactive oxygen species in macrophages and avoid diseases such as colitis and colorectal cancer caused by chronic inflammation. Associate Professor Xu of China Medical University found that the richness and diversity of intestinal flora in mice with GPx8 gene deletion would decrease.
Xu said that there are many bacteria in human intestines. If the immune system regards bacteria as pathogens, macrophages in the immune system will produce reactive oxygen species, which will also activate the protein caspase-4 and inflammatory body. In addition to recognizing various pathogens and danger signals, inflammatory bodies also produce cytokines and produce inflammatory reactions.
It was found that the lack of GPx8 could not inhibit the activation of caspase-4, so that the inflammatory reaction could not stop. Persistent chronic inflammation of the intestine is the main cause of colitis, Crohn's disease and colorectal cancer. However, the expression of GPx8 gene in many patients with ulcerative colitis is indeed low, which indicates that the deletion of this gene is closely related to colitis.
The research that GPx7 and GPx8 can inhibit excessive inflammatory reaction has been published in international journals.
The research team tested two drugs: one is to use small molecule drugs to remove excessive peroxide; Another method is to use inhibitors to inhibit the activation of caspase -4. The results show that these two drugs can inhibit excessive inflammatory reaction, and these inhibitors may become potential drugs to treat autoimmune and intestinal inflammatory diseases in the future. Related papers were published in the international journals Cell Report and EMBO Molecular Medicine respectively.
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