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New Approach To Attacking Alzheimer's Disease Studied

Researchers have developed an array of new chemicals that may attack Alzheimer's disease in a unique way. The compounds target a little understood enzyme called butyrylcholinesterase, which has recently been shown to be elevated in the brains of patients with AD.

Details about the research will appear in the Journal of Medicinal Chemistry, published by the American Chemical Society (ACS), the world's largest scientific society. The paper became available on the ACS Web May 4 and will be in the journal's May 20 print edition.

Alzheimer's disease is the fourth leading cause of death in Western countries and is a cause of severe dementia in at least four million Americans. Those over 85 years of age, the fastest growing portion of the U.S. population, have a fifty-fifty chance of developing the disease.

One characteristic of Alzheimer's disease is decreased amounts of acetylcholine, a brain signaling chemical which plays a critical role in memory processing. After doing its job, acetylcholine is normally inactivated by enzymes called cholinesterases, which come in two forms and are found throughout the body. The first, acetylcholinesterase (AChE), works at nerve endings; current Alzheimer's disease drugs aim to temporarily disable it. The role of the other form, butyrylcholinesterase (BChE), is largely unknown. "Consequently, there has been minimal interest (among drug makers) in the design, synthesis and development of butyrylcholinesterase inhibitors," says the study's co-author Nigel H. Greig, Ph.D., from the National Institute on Aging's Intramural Research Program. The Institute's Qian-sheng Yu, Ph.D., is lead author on the paper.

While some current drugs randomly inhibit both AChE and BChE, Greig says those tend to have more side effects. He adds that "the present study represents the first to develop highly selective inhibitors of BChE alone with appropriate characteristics for use in animals and humans." Recent laboratory studies h
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Contact: Charmayne Marsh
y_marsh@acs.org
202-872-4445
American Chemical Society
5-May-1999


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