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Scientists Find Enzyme That Kills Alzheimer's Protein

Enzyme that kills Alzheimer's protein

Scientists have been looking for a killer, and they may have found one. At Mayo Clinic in Jacksonville, Florida, researchers discovered an enzyme that has the ability to kill an Alzheimer's protein called beta-amyloid.

How does an Alzheimer protein killer work?

Experts generally agree that beta-amyloids play a significant role in Alzheimer's disease, a thus-far incurable brain disorder that affects an estimated 5.4 million Americans and 36 million people around the world. By 2030, the number of cases is estimated to be 65.7 million.

Beta-amyloids are pieces of a larger protein called amyloid precursor protein (APP), which is found in many tissues but mainly in the synapses of nerve cells, like those in the brain. The exact functions of APP are not known, but they are believed to be involved in the formation of synapses and brain changes.

APP is fragmented by the actions of an enzyme called BACE1, and the result is the formation of protein pieces called beta-amyloids. While healthy brains can eliminate beta-amyloids, they accumulate and form hard plaques in people who have Alzheimer's disease.

Surprisingly, scientists discovered that an enzyme similar to BACE1, called BACE2, undoes the actions of BACE1. To put it another way, "BACE1 giveth, while BACE2 taketh away," according to the study's leader and neuroscientist, Malcolm A. Leissring, PhD.

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The research team scoured through hundreds of enzymes before they found one capable of reducing beta-amyloid more effectively than any others. But this is not the first time BACE2 has been shown to have killer instincts.

Previous research revealed that BACE2 can prevent production of beta-amyloids by slicing APPs at a location different from that of BACE1. However, this action takes place outside the brain, and so it does not have an impact on Alzheimer's disease.

This new discovery about BACE2 is important for several reasons. One, it highlights the positive importance of BACE2 and indicates that damage to this enzyme might increase a person's risk of developing Alzheimer's disease.

Two, it suggests BACE2 may be an "attractive candidate for gene therapy to treat Alzheimer's disease," according to Samer Abdul-Hay, PhD, a neuroscientist and the study's first author. Three, it makes researchers aware that some drugs currently in use, such as some used to treat human immunodeficiency virus (HIV), might hinder the activity of enzymes similar to BACE2 and thus increase the risk of Alzheimer's disease.

Prevention and effective treatment of Alzheimer's disease is still not a reality, but scientists are making progress. This latest discovery of an enzyme that kills Alzheimer proteins is an example of that effort.

Abdul-Hay SO et al. Identification of BACE2 as an avid SZ-amyloid degrading protease. Molecular Neurogeneration 2012; 7:46.
Alzheimer's Disease Research

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