NEW YORK, Oct 21 (Reuters Health) -- US scientists believe they have isolated the elusive enzyme responsible for the build-up of protein plaques in the brain, a hallmark of Alzheimer's disease. The discovery could lead to new treatments for Alzheimer's disease as well as ways to determine who may be at risk for developing the disease.
Dr. Martin Citron from Amgen, Inc., a biotechnology company based in Thousand Oaks, California, and colleagues report their discovery in the October 22nd issue of the journal Science.
It is believed that plaque build-up occurs when a protein called amyloid precursor protein (APP) is freed or 'cleaved' by two enzymes, namely beta-secretase and gamma-secretase. Scientists "know what these enzymes should look like, where they should be, and where and how they cleave APP, but their exact identity has remained a mystery," according to a press release from Science.
Over the past several years, numerous research groups have described 'candidate' enzymes for the elusive beta-secretase enzyme, but most have "failed to stand the test of time," according to an editorial in Science.
Citron and colleagues believe they have solved the mystery. They cloned and characterized an enzyme or protease that is associated with increased levels of cleaved APP. This enzyme, known as BACE (for beta-site APP-cleaving enzyme), exhibits all the known characteristics of beta-secretase.
According to the team, overexpression of BACE increases the amount of APP and plaque-forming beta amyloid peptides, particularly in neurons, or nerve cells. Inhibition of BACE, on the other hand, decreases the amount of APP and beta-amyloid freed by beta-secretase.
Citron and colleagues say studies looking at the activity of BACE in patients with Alzheimer's disease are needed.
Drugs that block the activity of BACE may prove useful in the treatment of patients with Alzheimer's disease, they add.
