Reelin and beta-Amyloid

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego. ______________________________________

The layering of neurons in the developing brain requires Reelin, a protein located on the outside of the cells. Reelin, also acts as a "green light", stimulating neurons to respond more strongly to their neighbors' signals. A recent study showed that applying Reelin directly to brain slices from mice prevents excess beta-amyloid from completely silencing nerves. In the study conducted using mouse models, the researchers determined that Reelin and beta-amyloid interact with the same receptor, (the NMDA receptor), which plays an important role in coordinating chemical signals between adjacent neurons.

They found that Reelin activates and strengthens the response of the NMDA receptor. In the presence of too much beta-amyloid, the receptor goes back 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.

More work will be needed to see if Reelin can be used as a potential treatment in AD.

Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15938-43.