The “super brain cops”, the microgliocytes, are implicated in Alzheimer’s disease. They lose their effectiveness because of a receptor, EP2, which boosts the formation of beta amyloid.
A major advance in the understanding of Alzheimer’s disease. The death of nerve cells, seen in sick people, is caused by the failure of other cells that act as “super brain cops.” A team from Stanford University (California, United States) is behind this major discovery, the results of which have been published in the Journal of Clinical Investigation.
Cleaning, defense, appeasement …
It is an established fact, in Alzheimer’s patients, the nerve cells are destroyed little by little, under the action of the deposits of amyloid plaque. If these plaques form, it is because other cells, the microgliocytes, are losing their effectiveness. These cells have a function similar to immune cells. They monitor any activity or suspicious product, protect the brain from bacteria and viruses by “swallowing” them, soothe inflammation, collect cellular and molecular waste … in particular the beta amyloid protein, known for its action in Alzheimer’s disease.
“Microgliocytes are the brain’s super cops,” summarizes Katrin Andreasson, lead author of the study. “The microgliocytes are supposed, from the start, to constantly cleanse beta amyloid and keep the reins of inflammation. If they lose their ability to function, you lose control. Beta amyloid builds up in the brain, resulting in toxic inflammation. “
Successful tests in mice
The Stanford team discovered that microgliocytes lose their efficiency because of a receptor on their surface: EP2. When active, it binds to another substance, prostaglandin E2 (PGE2). To reach these conclusions, the researchers used mice. Some of them were genetically modified to develop an animal equivalent of Alzheimer’s disease, the others were normal. In the presence of beta amyloid, the microgliocytes of young and normal mice calmly respond to the threat, and eradicate it. But in “old” mice, the reaction is quite different. Inflammation explodes, EP2 activity skyrockets … while the production of enzymes that destroy beta amyloid fall sharply. In contrast, in mice manipulated not to express the EP2 receptor, memory loss and learning difficulties are not manifested.
These results are interesting for two reasons. On the one hand, they provide a better understanding of the mechanism of action of Alzheimer’s disease. On the other hand, they offer a possible explanation for the link between nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, and reduced risk of Alzheimer’s. These drugs block the expression of two enzymes (COX-1 and COX-2), which create a molecule capable of converting into prostaglandin E2… This same molecule which triggers the EP2 receptor and regulates inflammation in the brain.
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