Blocking Specific Protein Found to Allow Brain's Own Immune System To Prevent Neurodegeneration

 Alzheimer's Disease  

Microglia cells in the brain chew up toxic substances and cell debris, calm inflammation and make nerve-cell-nurturing substances. New research shows that keeping them on the job may prevent neurodegeneration and Alzheimer's disease.

Alzheimer's could be prevented and even cured by boosting the brain's own immune response, scientists at Stanford University believe.

Researchers discovered that nerve cells die because cells which are supposed to clear the brain of bacteria, viruses and dangerous deposits, stop working.

These specialized nerve cells, called microglia make up about 10-15 percent of all the cells in the brain, actually resemble immune cells considerably more than they do nerve cells. Microglia function properly when people are young, but when they age, a single protein called EP2 stops them operating efficiently.

"Microglia are the brain’s beat cops. Our experiments show that keeping them on the right track counters memory loss and preserves healthy brain physiology."

Now scientists have shown that blocking EP2 allows the microglia to function normally again so they can deal with amyloid-beta plaques which damage nerve cells in Alzheimer's disease.
The researchers found that, in mice, blocking EP2 with a drug reversed memory loss and myriad other Alzheimer’s-like features in the animal models.

“Microglia are the brain’s beat cops,” said Dr Katrin Andreasson, Professor of neurology and neurological sciences at Stanford University School of Medicine.

“Our experiments show that keeping them on the right track counters memory loss and preserves healthy brain physiology.”

The study has been published in the Journal of Clinical Investigation.

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Microglial cells are the front-line soldiers of the brain, monitoring their surroundings for suspicious activities and materials by probing its local environment. If they spot trouble, microglia release substances that recruit other microglia to the scene, said Andreasson.

Microglia protect the brain against invading bacteria and viruses by gobbling them up also work as garbage collectors, chewing up dead cells and molecular debris strewn among living cells including clusters of amyloid-beta which aggregate as gummy deposits and break the connections between neurons, causing loss of memory and spatial awareness. These clusters are believed to play a substantial role in causing Alzheimer’s.

“The microglia are supposed to be, from the get-go, constantly clearing amyloid-beta, as well as keeping a lid on inflammation,” added Dr Andreasson. “If they lose their ability to function, things get out of control. A-beta builds up in the brain, inducing toxic inflammation.”

The scientists discovered that in young mice, the microglia kept the sticky plaques under control. But when experiments were done on older mice, the protein EP2 swung into action and stopped the microglia producing enzymes which digested the plaques.

Similarly mice which were genetically engineered not to have EP2 did not develop Alzheimer's disease, even when injected with a solution of amyloid-beta, suggesting that their cells were getting rid of the protein naturally.

In the mice who developed Alzheimer's-like disease, blocking EP2 reversed memory decline.
Now Stanford is hoping to produce a compound which only blocks EP2 to prevent unnecessary side effects.


SOURCE  Stanford University Top Image Hagop Kaneboughazian

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