BACE2 is the enzyme that has been found to destroy beta-amyloid, a toxic protein fragment that litters Alzherimer's patients' brains.
The most common memory disorder is Alzheimer's disease, affecting over 5.5 million Americans. Scientists have yet to discover any effective treatments, causing a great deal of financial trouble and personal strain.
However, previous research has shown that a drug that treats Alzheimer's symptoms may also slow down the progression of the disorder.
The new discovery, published in Molecular Neurodegeneration was made by a team at Mayo Clinic, led by Malcolm A. Leissring, Ph.D., a neuroscientist. The experts tested hundreds of enzymes to determine which could lower beta-amyloid levels. Out of all the enzymes analyzed, BACE2 proved to lower beta-amyloid the most effectively.
The authors were surprised with the results since BACE2 is related to another enzyme, known as BACE1, which produces beta-amyloid.
"Despite their close similarity, the two enzymes have completely opposite effects on beta-amyloid- BACE1 giveth, while BACE2 taketh away," Dr. Leissring explained.
Beta-amyloid is a part of a larger protein, known as APP. It is created by enzymes that cut APP at two places:
- The first cut is made by BACE1, which generates beta-amyloid
- BACE2 then cuts beta-amyloid into smaller pieces, which in turn, destroys it
Prior studies indicated that the levels of beta-amyloid can be lowered by BACE2, but with a different mechanism- by cutting APP at a different spot from BACE1. BACE2 cuts in the middle of the beta-amyloid portion, which stops beta-amyloid from being generated.
"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," Samer Abdul-Hay, Ph.D., first author and a neuroscientist at Mayo Clinic.
The findings indicate that the risk of Alzheimer's disease might be increased by impairments in BACE2. The results are of great value because certain prescribed drugs, such as antiviral drugs treating human immunodeficiency virus (HIV), work by inhibiting enzymes closely related to BACE2.
According to the researchers, the newly discovered mechanism, the destroying of beta-amyloid, is likely relevant to the disease, unlike the mechanism previously identified. This is because the second mechanism, which involves BACE2 cutting APP, does not occur in the brain.
The team is further exploring their research by using a mouse model to determine whether the risk of Alzheimer's is increased by using BACE2 to block beta-amyloid destruction.
Written by Sarah Glynn