Dry cleaning for the brain
Blocking one protein returned the old mice intelligence
Sergey Kolenov, Hi-tech+
We are talking about the CD22 protein selected from 3,000 candidates. It stimulates the work of microglia – the "cleaning system" of the brain. Perhaps someday an attack on this protein will help treat Alzheimer's disease and other neurodegenerative diseases.
With age, the working capacity of the brain decreases, but the exact mechanisms of this process are still unclear. According to neuroscientist Tony Viss-Corey, one of its causes may be changes in microglia – immune cells of the brain. Among other things, microglia works as a purification system, absorbing metabolic waste and waste proteins. In an aging brain, its effectiveness decreases.
It is likely that this process contributes to the age-related decline of cognitive functions and the development of neurodegenerative diseases. This assumption is supported by the fact that some of the genes associated with Alzheimer's disease in the brain are active only in microglia. In addition, a number of such diseases are characterized by incorrect gene expression in microglia.
Researchers from Stanford University, whose work is described in the Stanford Medicine Blocking protein's activity restores cognition in old mice, have found a way to "fix" the brain cleaning system. To begin with, they studied how genes affect the ability of microglia to phagocytosis – the capture and digestion of molecules.
A huge amount of work has been done: scientists have consistently "turned on" and "turned off" about 3,000 genes to understand how each of them affects the intensity of phagocytosis.
In a parallel experiment, the team determined which of these genes are more active in the hippocampal microglia of young mice by comparing them with older individuals.
Surprisingly, by comparing the results of the two researchers, the team obtained only one CD22 gene, which suppresses phagocytosis and significantly changes its activity with age. His "shutdown" returned the "cleaning system" to normal.
In the next experiment, it was found that the concentration of CD22 protein in old mice was three times higher than in their young relatives.
Since CD22 is a surface protein, it can be affected by antibodies. That's exactly what the team did. On one side of the mouse hippocampus, the researchers injected antibodies to CD22, and on the other – similar, but unable to bind to this protein. In addition to antibodies, myelin "garbage" labeled with a fluorescent label was injected into the hippocampus.
After 48 hours, the concentration of "garbage" turned out to be much lower on the side where antibodies to CD22 were injected.
A drawing from an article in Nature – VM.
Similar results were obtained if myelin was replaced with beta-amyloids and alpha-synucleins, which are associated with Alzheimer's disease and Parkinson's disease, respectively.
Continuous injections of antibodies for a month reversed the intellectual extinction of old mice. In memory and learning tests, the treated individuals outperformed relatives from the control group.
The article by Pluvinage et al. CD22 blockade restores homeostatic microglial phagocytosis in aging brains is published in the journal Nature – VM.
The human genome also contains the CD22 gene, which makes it a promising target for the fight against neurodegenerative diseases. However, it should be remembered that not all therapeutic techniques confirmed in mice will necessarily work for humans.
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