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Protein That Controls Nerve Regeneration Also May Control Alzheimer's Disease Progression, Cleveland Clinic Researchers Say

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www.ProHealth.com • August 2, 2004


CLEVELAND, Aug. 2 /PRNewswire/ --

Researchers in the Department of Neurosciences at The Cleveland Clinic Lerner Research Institute have found that Nogo, a protein known for its ability to regulate nerve regeneration, may control the progression of Alzheimer's disease. This research, led by Riqiang Yan, M.D., will be published in the September issue of Nature Medicine. The study appears Aug. 1 on the Nature Medicine website, http://www.nature.com/nm .

"These findings are significant because they identify a potential therapeutic target that may slow the progression of Alzheimer's disease," Dr. Yan said. Alzheimer's patients have an excessive accumulation of amyloid plaque in their brains. A small protein in this plaque, called beta amyloid, is widely considered a culprit for the disease. Beta amyloid is produced through the activity of an enzyme called beta-secretase, or BACE1.

Dr. Yan is best known in the Alzheimer's research community as the co-discoverer of BACE1. Development of drugs that inhibit BACE1 has become a major focus in many large pharmaceutical companies because such drugs could reduce beta amyloid production and, in turn, slow the progression of Alzheimer's disease. In their current research, Dr. Yan and colleagues identified a molecule that interacts with BACE1 to decrease beta amyloid production. This molecule is called reticulon, or NOGO.

The scientists now are seeking ways to increase this interaction and delay the progression of Alzheimer's disease as effectively as possible. "It has been a huge challenge to discover small-molecule drugs to inhibit BACE1 activity due to the molecular nature of this protein," Dr. Yan said. "Purposely controlling the levels of reticulon in patients using small-molecule drugs may offer an alternative method to reduce beta amyloid production and Alzheimer's progression."

Dr. Yan joined the Lerner Research Institute about one year ago to continue his studies in BACE1 and this new discovery of reticulon proteins. The Lerner Research Institute, home to The Cleveland Clinic's basic research departments, houses approximately 130 principal investigators and their teams who are pursuing a wide range of biomedical questions. With total annual research expenditures exceeding $150 million from federal agencies, non-federal societies and associations, and endowment funds, the Lerner Research Institute is the fifth largest research institute in the country.

The Department of Neurosciences is chaired by Bruce Trapp, Ph.D., and comprises a core of internationally recognized scientists who investigate the cellular and molecular biology of brain development and neuronal and glial function. This department has recently begun to expand research into Alzheimer's disease.

The Cleveland Clinic Foundation, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. The Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names The Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,200 full-time salaried physicians at The Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2003, patients came for treatment from every state and from nearly 90 countries. The Cleveland Clinic website address is http://www.clevelandclinic.org .

SOURCE The Cleveland Clinic Foundation Web Site: http://www.clevelandclinic.org http://www.nature.com/nm



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