Alzheimer’s researchers have identified an enzyme that destroys beta-amyloid, a toxic protein fragment that accumulates and forms hardened plaques in the brains of patients with the disease.
Scientists from Mayo Clinic in Florida say the enzyme, known as BACE2, may be an important weapon against Alzheimer’s, which affects more than 5.5 million Americans.
Mayo Clinic findings were published online Sept. 17 in the science journal Molecular Neurodegeneration.
The Mayo research team, led by neuroscientist Malcolm A. Leissring, made the discovery by testing hundreds of enzymes for the ability to lower beta-amyloid levels, according to a clinic press release. BACE2 was found to lower beta-amyloid more effectively than all other enzymes tested. Researchers said the discovery is interesting because BACE2 is closely related to another enzyme, known as BACE1, which is involved in producing beta-amyloid.
“Despite their close similarity, the two enzymes have completely opposite effects on beta-amyloid — BACE1 giveth, while BACE2 taketh away,” Leissring said in the statement.
Beta-amyloid is a fragment of a larger protein, called amyloid precursor protein (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 through 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,” says Samer Abdul-Hay, another Mayo Clinic neuroscientist who worked on the research.
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.
Although BACE2 can lower beta-amyloid by two distinct mechanisms, only the newly discovered mechanism — beta-amyloid destruction — is likely relevant to the disease, the researchers note. This is because the second mechanism, which involves BACE2 cutting APP, does not occur in the brain.
The researchers have obtained a National Institutes of Health grant to study whether blocking beta-amyloid destruction by BACE2 can increase the risk for Alzheimer’s disease in a mouse model of the disease.
Citation: Mayo Clinic. “New enzyme to fight Alzheimer’s disease identified.” ScienceDaily, 17 Sep. 2012. http://www.sciencedaily.com/releases/2012/09/120917151723.htm