New findings about brain proteins suggest possible way to fight Alzheimer's

October 6, 2009,
Here are Drs. Joachim Herz (right), Murat Durakoglugil of UT Southwestern Medical Center. Credit: UT Southwestern Medical Center

The action of a small protein that is a major villain in Alzheimer's disease can be counterbalanced with another brain protein, researchers at UT Southwestern Medical Center have found in an animal study.

The findings, available online in the journal , suggest a promising new tactic against the devastating illness, the researchers said.

The harmful protein, called beta-amyloid, is found in the brain and, when functioning properly, suppresses nerve activity involved with memory and . 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. People with Alzheimer's disease, however, accumulate too much beta-amyloid - the traffic light gets stuck on "red" and nerve cells become less responsive.

Another , called Reelin, acts as a "green light," stimulating nerve cells to respond more strongly to their neighbors' signals.

The new study shows 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, professor of and neuroscience at UT Southwestern and the study's senior author.

In the study, the researchers recorded electrical currents in the mouse hippocampus, an area of the brain associated with learning and . From their experiments 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 .

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.

Dr. Herz said the study is especially important because this mechanism involves another protein involved in Alzheimer's 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.

"These 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," Dr. Herz said. "This 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."

The researchers are currently studying the role of ApoE4 in this mechanism. Mimicking or preserving normal Reelin function to stimulate the ApoE receptors might provide a path to stave off the disease, Dr. Herz said.

Source: UT Southwestern Medical Center (news : web)

Related Stories

Recommended for you

Spare parts from small parts: Novel scaffolds to grow muscle

February 20, 2018
Australian biomedical engineers have successfully produced a 3D material that mimics nature to transform cells into muscle.

Clues to obesity's roots found in brain's quality control process

February 20, 2018
Deep in the middle of our heads lies a tiny nub of nerve cells that play a key role in how hungry we feel, how much we eat, and how much weight we gain.

Study looks at how newly discovered gene helps grow blood vessels

February 19, 2018
A new study published today found that a newly discovered gene helps grow blood vessels when it senses inadequate blood flow to tissues.

Scientists produce human intestinal lining that re-creates living tissue inside organ-chip

February 16, 2018
Investigators have demonstrated how cells of a human intestinal lining created outside an individual's body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing ...

Data wave hits health care

February 16, 2018
Technology used by Facebook, Google and Amazon to turn spoken language into text, recognize faces and target advertising could help doctors fight one of the deadliest infections in American hospitals.

Researcher explains how statistics, neuroscience improve anesthesiology

February 16, 2018
It's intuitive that anesthesia operates in the brain, but the standard protocol among anesthesiologists when monitoring and dosing patients during surgery is to rely on indirect signs of arousal like movement, and changes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.