Brain Protein Could be Used to Fight Beta Amyloid in Alzheimer’s

By on October 7, 2009

Beta Amyloid Researchers have found in an animal study that the action of the harmful protein beta-amyloid in Alzheimer’s disease can be counterbalanced with another brain protein.

Beta-amyloid is found in the brain and when functioning properly suppresses nerve activity involved with memory and learning. Its normal function can be likened to a red traffic light, restraining nerve cells from getting overexcited when they receive stimulating signals from neighboring cells. Alzheimer’s disease patients accumulate too much beta-amyloid, the traffic light gets stuck on “red” and nerve cells become less responsive.

Another brain protein, called Reelin, acts as a “green light,” stimulating nerve cells to respond more strongly to their neighbors’ signals.

This study showed that applying Reelin directly to brain slices from mice prevents excess beta-amyloid from completely silencing nerves.

“If we can identify a mechanism to keep the nerve cells functioning strongly, that might provide a way to fight Alzheimer’s disease,” said Dr. Joachim Herz, the study’s senior author.

The researchers recorded electrical currents in the mouse hippocampus, an area of the brain associated with learning and memory. They determined that Reelin and beta-amyloid interact with the same protein complex, called an NMDA receptor, which plays an important role in coordinating chemical signals between adjacent nerve cells.

They found that Reelin activates and strengthens the response of the NMDA receptor. In the presence of too much beta-amyloid, the receptor migrates into the cell, reducing the cell’s sensitivity to incoming signals. By contrast, in strong concentrations of Reelin, the receptor remains active and the cell has the green light to continue receiving normally.

This mechanism involves another protein involved in Alzheimer’s disease called ApoE4, which is the primary risk factor for the most frequent late-onset form of the disease. The receptor that binds to ApeE molecules also binds to Reelin, and is part of the red-light/green-light complex that controls the sensitivity of the NMDA receptors.

The results imply that Reelin, ApoE and beta-amyloid converge on the same molecular mechanism, which is critical in the Alzheimer’s disease process, and Reelin may be a common factor to fight both beta-amyloid and mutated ApoE. The study establishes a rationale that ApoE receptors have an action that can keep the Alzheimer’s disease process at bay by preventing damage in the first place.

References:
1. Joachim Herz, et al. Reelin signaling antagonizes ?-amyloid at the synapse. PNAS 2009 106:15938-15943; doi:10.1073/pnas.0908176106.

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