| Return to News Index |  |
Return to Home page |
WEDNESDAY, Dec. 1 (HealthSCOUT) -- Two teams of American scientists have finally discovered a long-sought piece of the Alzheimer's puzzle.
The latest issue of Nature reports that researchers based in California and Michigan have independently discovered an enzyme linked to the presence of "amyloid plaques." The plaques build up in the brains of Alzheimer's patients and are thought to cause the disease's trademark mental deterioration.
These plaques are deposits of pieces of protein known as amyloid-beta. The fragments come about when enzymes called proteases cut a large protein called amyloid precursor protein (APP) in two places: the beta-site and the gamma-site. Scientists have been searching for these enzymes because drugs to dampen their activity may help fight Alzheimer's.
Now, the researchers have identified one of the enzymes, called Asp2 or beta-site APP-cleaving enzyme (BASE). The first study, from Pharmacia & Upjohn in Kalamazoo, Mich., drew on the experience of two team members who had worked with HIV enzymes. HIV is the virus that causes AIDS. They suspected that the protease they were looking for was part of a family of aspartyl proteases, similar to those involved with HIV, but it had to be a protease never before identified in humans.
According to the study's senior author, Mark Gurney, they turned to the human genome to find the protease. Scientists knew that there are 11 human genes that contain information for aspartyl proteases, seven of which have already been identified. Gurney and his colleagues tested each of the remaining four genes until they finally found the one that sparked the protease production.
"The Asp2 protease makes the first cut, and then another protease that we still haven't identified makes the second cut, then that peptide gets deposited in the brain," says Gurney. Gurney and his colleagues don't know yet whether the protease does anything else in the body, but they do know that it's also found in the pancreas."The excitement here is that we now have an enzyme which, if we can block its function with a drug, we may be able to prevent the formation of the amyloid-beta peptide," says Gurney, which could either prevent or treat Alzheimer's disease. "That process should go pretty rapidly, and then [we'd] want to take that into clinical trials."
"You want to suppress the activity of this enzyme by some amount on a chronic basis," says Sinha. He adds that it may be of greater use as a therapy for patients still in the early stages of disease. Between them, Gurney and Sinha estimate that a clinically available drug is between two and five years away.In a related editorial, Dr. Bart De Strooper, a professor of human genetics at the Katholieke Universiteit Leuven in Leuven, Belgium, says that it may not be necessary to completely turn off this enzyme. "If we can interfere with the function for 30-50 percent, then probably we can sufficiently inhibit the production of this peptide," he says, adding that recent studies have shown that amyloid protein is produced in normal conditions. "In Alzheimer's disease, you get an increased production of this peptide, so probably if you can decrease this production to a normal physiological level, then we can at least postpone Alzheimer's disease.""The nice thing about working in this area is that there are animal models that are available," says Gurney, referring to a recently developed genetically altered mouse that produces the human APP gene. If a new drug works in these mice, he says, there's a very good chance that it could work in humans.
| Return to News Index | |
Return to Home page |