Oklahoma City, OK – Scientists at the Oklahoma Medical Research Foundation (OMRF) have positively identified the enzyme that is directly related to Alzheimer’s disease. The Protein Studies Program, led by Dr. Jordan Tang, was able to pinpoint the “beta secretase” enzyme and have named it “memapsin 2.” The over-activity this protein-cutting enzyme, called a protease, is responsible for the plaques and tangles which disrupt brain activity and cause Alzheimer’s disease. A paper describing Tang’s discovery has been published in today’s Proceedings of the National Academy of Science.
“Dr. Tang’s finding is the most exciting discovery I have experienced during my tenure at OMRF,” said foundation president J. Donald Capra, M.D. “By identifying the enzyme which is responsible for Alzheimer’s disease, we are now able to study the protease and ultimately design a drug which will stop the progression of the disease.”
In the 1980’s, scientists discovered that the Alzheimer’s plaques were made primarily of a deposit of a small protein called beta-amyloid (A-beta). As A-beta accumulates, it begins to disrupt brain function and kill neurons. When brain cells die, they cannot be replaced like other cells and symptoms of Alzheimer’s becomes evident. As more neurons die, the brain cannot signal the body to conduct basic functions, eventually leading to dementia. Thus, the question “where does A-beta come from and how do we dispose of it” has been the key to understanding and treating Alzheimer’s disease.
Scientists then discovered that A-beta was a part of a larger protein called amyloid precursor protein, (APP). APP is present in all people and is usually cut up by proteases, which are the enzymes our body uses to cut proteins. The “beta secretase” site was one of the places where scientists theorized that the cutting of APP took place, thus creating the A-beta and Alzheimer’s plaques. However, scientists had not been able to positively identify the actual protease.
Dr. Tang and two other principal members of the scientific team — Drs. Xin-Li Lin and Gerald Koelsch – identified the protease now called memapsin 2. Moreover, the OMRF team was able to “express,” or reproduce, memapsin 2 in large quantities, allowing the scientists to thoroughly study the important properties of the protease.
Tang noted that while other groups had positively identified the beta secretase site late in 1999, they could not express the enzyme and study it in as great detail as the scientists at OMRF. “Since we can produce a significant amount of memapsin 2 in our laboratories, we will be able to determine its structure and study how the protease operates and eventually design an inhibitor to stop it. There is now hope in our fight against Alzheimer’s disease,” he said.
Memapsin 2 is a specific kind of enzyme called aspartic proteases, for which Dr. Tang and his group of scientists have received international recognition for their important contributions through the years. In fact, the pioneering discovery of the first inhibitor for this kind of protease was first done by Dr. Tang’s laboratory in the 1970’s. The principles discovered through the study of aspartic proteases were later applied to the making of successful inhibitor drugs to stop HIV in AIDS patients. Tang and his colleagues at OMRF are optimistic that this same kind of principle will be applied to make inhibitor drugs to stop memapsin 2 and the progression of Alzheimer’s disease.
“It is quite possible that we will soon develop the medical technology to detect Alzheimer’s before its onset,” said Tang. “The discovery of memapsin 2 and the study of this protease are the most significant steps science has taken to understand and control this disease.”
Chartered in 1946, OMRF is a private, non-profit biomedical research institution which employs over 400 scientists, physicians, technicians, and administrative and support personnel. Along with Alzheimer’s disease, OMRF focuses on several critical areas of research: cancer, heart disease, diabetes, lupus and other autoimmune diseases, stroke, AIDS, children’s diseases, and genetic disorders.
Additional information, including copies of Dr. Tang’s paper and a summary of the discovery, are available upon request.
Description of Alzheimer’s discovery
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