AD immunotherapy breakthrough! Inhibition of CD22 enhances phagocytic activity of microglia April 08, 2019 Source: Singularity Network If a city's garbage disposal station fails, it will surely float "smelly" and disturb residents. And if there is a problem with the "garbage disposal station" in one's body, the functions of the body will be affected. Especially in the brain, the garbage accumulates much, and the brain becomes "slow". The neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are all related to the accumulation of "garbage" protein in the brain. Microglia are important immune cells in the brain and serve as a cleansing task. Today, the singular cake will tell you a little about the problem of microglia. How to repair it? Dr. Tony Wyss-Coray of Stanford University and his team published in the top journal Nature, they successfully found the protein CD22, which regulates the "clean" ability of microglia, and inhibits CD22 to restore aging mice. The cleansing function of microglia reduces the "garbage" protein in the brains of Alzheimer's disease mice and Parkinson's disease mice, and improves mouse cognition [1]. Important notice, Dr. Wyss-Coray brand garbage station maintenance factory is about to open, and the singular cake will bring you the latest reports on the front line. The microglia, a garbage station, has a long life and plays an irreplaceable role in almost all life cycles [2, 3]. During the development of the brain, if the neurons are connected or the protein is wrong, microglia are needed to clean them up [4, 5]. In neurodegenerative diseases and other aging-related diseases, the normal cleansing function of microglia is seriously disturbed, and the well-functioning protein is "eaten" for no reason, the cleaned error protein is not cleaned, and a large amount of myelin The accumulation of debris and proteins has ruined a wave of researchers. The system is faulty and cannot be restarted. What should I do? During the long working life of microglia, the transcription levels of various genes have also changed with age [6,7], but the scope of their respective duties has not been carefully studied. Dr. Wyss-Coray decided to start with the details, a gene and a genetic study. Dr. Wyss-Coray picked about 3,000 genes encoding proteins and knocked them out. It was found that knocking out the CD22 protein gene can significantly promote the phagocytosis of mouse microglia. Further experiments showed that the expression of CD22 on the surface of glial cells in aging mice was three times that of young mice! It is a proper aging-related phenotype. Microglia expressing CD22 is almost absent in the young brain, but in the old brain it is full of stars (see photo). After fluorescently labeling microglia and CD22, respectively, the researchers also found that in the central nervous system of mice, only microglia appeared to express CD22. This is much easier to do, inhibiting CD22, and is not afraid of any effect on other cells. The researchers injected CD22 antibodies and immunoglobulins (IgG) into the brain of mice to assess their effects on microglia clearance. After 48 hours, CD22 antibody treatment significantly increased the phagocytic capacity of senescent mouse microglia compared to IgG and did not significantly affect the central nervous system of young mice. Knocking out the CD22 gene can have the same effect. In Alzheimer's disease model mice and Parkinson's disease model mice, the addition of CD22 antibody can also promote the phagocytosis of microglia, whether it is beta amyloid or alpha synuclein fiber, the number is obvious Reduced, which are typical features of Alzheimer's disease and Parkinson's disease, respectively. At the same time, blocking CD22 can also "retain" the youthfulness of microglia and help it maintain its homeostasis. Continuous injection of CD22 antibody into the brain of mice for one month, the gene expression of microglia was significantly more "young" than those injected with IgG or untreated control, chemokines associated with hippocampal damage Less expression. The hippocampus is protected and the time is very gentle on the mice. Even if the age is old, the memory and learning ability will be better than those without CD22 antibody. To sum up, CD22 is a negative regulator of microglia phagocytosis. It is up-regulated with aging, inhibiting the phagocytosis of microglia, leading to the shutdown of the “garbage station†and affecting the normal function of the brain. Inhibition of CD22 can delay aging-related dysfunction and neurodegenerative diseases. However, CD22 is not a complete negative role. Seven days after the birth of the mouse, CD22 appears in the microglia, preventing the microglia from being "fired" and clearing out those neurons that are not fully developed. However, during the aging process, this protective mechanism was erroneously activated, which in turn allowed myelin fragments and “junk†proteins to occupy the “highlandsâ€. This tells us that the right time needs to do the right thing. For example, at 10:30 every night, you should turn on your mobile phone to see the push of the singular cake. Fresh Half Shell Mussel Meat,Half Shell Mussel Meat,Frozen Cooked Mussel Meat,Frozen Mussel Shengsi Xiangyuan Aquatic Products Co.,Ltd., , https://www.xiangyuan-aquatic.com
Dr. Tony Wyss-Coray, also an old friend. 
Green: microglia; red: CD22 red-green arrow is a microglia expressing CD22 
CD22 antibody treatment (green) significantly reduces beta amyloid 
I want to make time slower, singing doesn't work, CD22 is going to work.