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Alzheimers And Other Dementias - Enzyme Could Play Role in Treating Alzheimer's
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Enzyme Could Play Role in Treating Alzheimer's
(HealthDay News)
by By Steven Reinberg
HealthDay Reporter
Updated: Oct 11th 2006

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WEDNESDAY, Oct. 11 (HealthDay News) -- Manipulating an enzyme that dilutes amyloid-beta could lead to new drugs that reduce the abnormal levels of this protein in the brains of people with Alzheimer's disease, a new study suggests.

Insulin-degrading enzyme (IDE) is unusual because it can bind diverse substances together. Now researchers have determined the structure of IDE in four substances, including amyloid-beta, which is the plaque-forming protein structure found in the brains of Alzheimer's patients.

The findings are published in the Oct. 11 online edition of Nature.

"We have identified the three-dimensional structure of IDE," said lead researcher Wei-Jen Tang, an associate professor at the University of Chicago's Ben May Institute for Cancer Research.

This finding may lead to a way of preventing Alzheimer's disease and slowing its progression, Tang said. However, the research at this point is in its early states, he cautioned, meaning the prospect for drugs to treat Alzheimer's is a long way off.

In its study, Tang's team shows that IDE undergoes changes when it binds to proteins like insulin and amyloid-beta, forming an enclosed chamber shaped like a triangular prism.

"We have also found a way to make IDE degrade at a higher rate," Tang said. Mutations in IDE can cause the chamber to open, increasing the rate that IDE and amyloid-beta will break down by up to 40-fold, he said.

"This highlights the possibility that we can manipulate the enzyme [IDE] or even use the enzyme itself as a potential therapeutic agent," Tang said.

Knowing what IDE looks like and how it works may make it possible to develop drugs that act like IDE mutations. This, in turn, might help clear the accumulation of amyloid-beta found in the brains of Alzheimer's patients, Tang said.

One expert thinks these findings might help in discovering a drug to break down amyloid-beta in the brain.

"One potential therapy for Alzheimer's involves finding a drug that will help the brain to degrade poisonous clumps of a material called amyloid," said Dr. Sam Gandy, chairman of the medical and scientific advisory council at the Alzheimer's Association, and director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

IDE is an enzyme that can play such a role, Gandy said. "The new paper shows that IDE has some unusual properties that one would never have guessed. The new information could be useful in designing a medicine to stimulate IDE breakdown of amyloid. The unsuspected aspects of the way IDE acts may tell us how to achieve our goal while minimizing side effects," he said.

Another expert agrees that targeting IDE may be a potentially effective Alzheimer's therapy.

"Since IDE also regulates levels of important hormones, this approach has potential to cause side-effect problems. But there may be a therapeutic window where IDE could be increased just enough to tip the balance toward amyloid-beta clearance and slow down development of Alzheimer's without causing problems," said Greg M. Cole, a neuroscientist at the Greater Los Angeles VA Healthcare System, and associate director of the Alzheimer's Disease Research Center at the University of California, Los Angeles, David Geffen School of Medicine.

More information

To learn more, visit the Alzheimer's Association.