Newly found enzyme works two ways to fight Alzheimer’s

Alzheimer’s disease affects over 5.5 million Americans and is the most common memory disorder worldwide. But despite all the attention it receives, no effective treatment has been found – until now.

Researchers led by Dr.  Malcolm Leissring, a neuroscientist at Mayo Clinic in Fla., recently discovered an enzyme – dubbed BACE 2 – that cuts beta-amyloid, effectively destroying the toxic protein prevalent in patients struggling with Alzheimer’s.

The discovery is interesting because after testing hundreds of enzymes, the research team found that the BACE 2 enzyme was closely related to the enzyme involved in beta-amyloid production. This enzyme, known as BACE 1, involves the cutting of the larger protein APP into fragments, which essentially become the beta-amyloid.

With the introduction of the BACE 2 enzyme, beta-amyloid is cut again, which ultimately destroys the harmful protein. In a second mechanism, BACE 2 was introduced to APP at a different spot and effectively cut the middle of the beta-amyloid, preventing any further production of the protein.

"The fact that BACE 2 can lower beta-amyloid by two distinct mechanisms makes this enzyme an especially attractive candidate for gene therapy to treat Alzheimer's disease," reported first author Dr. Samer Abdul-Hay, fellow neuroscientist at Mayo Clinic in Florida.

Certain drugs in clinical use – such as antiviral drugs used to treat HIV – work by impairing similar enzymes to BACE 2.  The results of this study indicate that such drugs might have a potential side effect of increasing the risk of Alzheimer’s disease.

As of now, the researchers hope to get a better understanding of the BACE 2 enzyme’s first mechanism, which destroys beta-amyloid – the mechanism most likely relevant to treating Alzheimer’s.  The second mechanism that involves cutting APP does not occur in the brain.  Leissring and his colleagues will further their research by studying whether or not blocking BACE 2 bet-amyloid destruction increases the risk for Alzheimer’s in mice.

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