By Merritt McKinney
NEW YORK, Jun 07 (Reuters Health) - Scientists have pinned down the identity
of an elusive enzyme believed to play a role in the development of Alzheimer's
disease. The enzyme may be a good target for drugs to treat Alzheimer's, one of
the study's authors told Reuters Health in an interview.
According to Dr. Stephen J. Gardell, a researcher at Merck Research
Laboratories in West Point, Pennsylvania, scientists are in "the midst of a
campaign" to develop drugs that will block the development of Alzheimer's
disease. Referring to the discovery made by his team, he said, "We have helped
to define the target for a possible therapeutic agent."
But Gardell cautioned that the search for drugs to treat the disease is
still in the early stages.
For years, a protein fragment called beta-amyloid peptide has been thought
to play a role in the formation of plaques that develop in the brains of people
with Alzheimer's disease. This peptide is formed when two
enzymes--beta-secretase and gamma-secretase--clip off portions of a protein
called amyloid precursor protein. The exact identities of both enzymes remained
a mystery, however, until last year, when the identity of beta-secretase was
identified.
Now Gardell and his colleagues report in the June 8th issue of the journal
Nature that they have identified the other enzyme. They suspect that a protein
called presenilin is the gamma-secretase, or at least its source.
In the study, Gardell and his colleagues developed special compounds that
attacked gamma-secretase when they were exposed to light. When the researchers
tested these gamma-inhibitors, the compounds targeted presenilins. This suggests
that presenilins may be the source of gamma-secretase, Gardell said.
But despite the discovery, developing drugs that slow down Alzheimer's by
blocking these enzymes will be a tedious process, since it is unlikely that the
compounds used in the lab will work in people, according to Dr. Bart De
Strooper, of the Flanders Interuniversitary Institute for Biotechnology in
Leuven, Belgium.
But De Strooper notes in an editorial that accompanies the study, "The good
news is that pharmaceutical companies now have another defined target for their
drug-discovery machineries."
