Enzyme Found That Destroys Alzheimer’s Plaques
The enzyme is known as BACE2 and was found to lower beta-amyloid more effectively than hundreds of other enzymes. Although closely related to BACE1 — the enzyme responsible for creating beta-amyloid — BACE2 has the opposite effect.
The Mayo research team, led by Malcolm A. Leissring, Ph.D., tested hundreds of enzymes to ascertain their effect on beta-amyloids.
“Despite their close similarity, the two enzymes have completely opposite effects on beta-amyloid — BACE1 giveth, while BACE2 taketh away,” Leissring said.
Beta-amyloid is a fragment of a larger protein, known as APP, and is produced by enzymes that cut APP at two places.
BACE1 is the enzyme responsible for making the first cut that generates beta-amyloid. The research showed that BACE2 cuts beta-amyloid into smaller pieces, thereby destroying it, instead.
Although other enzymes are known to break down beta-amyloid, BACE2 is particularly efficient at this function, the study found.
Previous work had shown that BACE2 can also lower beta-amyloid levels by a second mechanism: by cutting APP at a different spot from BACE1. BACE2 cuts in the middle of the beta-amyloid portion, which prevents beta-amyloid production.
“The fact that BACE2 can lower beta-amyloid by two distinct mechanisms makes this enzyme an especially attractive candidate for gene therapy to treat Alzheimer’s disease,” said first author Samer Abdul-Hay, Ph.D., a neuroscientist at Mayo Clinic in Florida.
The discovery suggests that impairments in BACE2 might increase the risk of Alzheimer’s disease. This is important because certain drugs in clinical use — for example, antiviral drugs used to treat human immunodeficiency virus (HIV) — work by inhibiting enzymes similar to BACE2.
Researchers say that although BACE2 can lower beta-amyloid by two distinct mechanisms, only the newly discovered mechanism — beta-amyloid destruction — is likely relevant to the disease. This is because the second mechanism, which involves BACE2 cutting APP, does not occur in the brain.
Alzheimer’s disease is the most common memory disorder, affecting more that 5.5 million people in the United States, yet researchers continue to search for an effective treatment of the devastating illness.
The next step in the research is for the investigators to study whether blocking beta-amyloid destruction by BACE2 increases the risk for Alzheimer’s disease in a mouse model of the disease.
Source: Mayo Clinic
Nauert PhD, R. (2012). Enzyme Found That Destroys Alzheimer’s Plaques. Psych Central. Retrieved on October 4, 2015, from http://psychcentral.com/news/2012/09/19/enzyme-found-that-destroys-alzheimers-plaques/44753.html