Oklahoma City, OK – The most recent development in OMRF’s study of Alzheimer’s disease will be published in Science on Friday, October 6, 2000. The paper discusses the three-dimensional crystal structure of memapsin 2 attached to an inhibitor, which was determined by scientists at OMRF. Memapsin 2 is one of the enzymes believed to be responsible for Alzheimer’s disease.
This finding is of “milestone significance” in Alzheimer’s research because it shows, in great structural detail, the way an inhibitor interacts with and disables the memapsin 2 enzyme. Such information will assist in the design and development of new drugs to control Alzheimer’s disease. The members of the research team primarily responsible for this discovery include Drs. Lin Hong, Gerald Koelsch, Xinli Lin, Shili Wu, Simon Terzyan, Arun K. Ghosh, Xuenjun C. Zhang, and Jordan Tang, all Ph.Ds at OMRF.
“The crystal structure of memapsin 2 with an inhibitor is a road map to better inhibitor drugs,” said Dr. Tang, Head of the Protein Studies department at OMRF. “The publication of this structure will allow many research teams, including those in pharmaceutical companies, to develop new drugs according to this road map.”
The crystal structure is the latest development in Alzheimer’s research at OMRF. In February of this year, Dr. Tang’s lab announced the initial discovery of memapsin 2 and by April, the team had designed an inhibitor to stop the enzyme’s cutting action.
Memapsin 2 is one of two protein-cutting enzymes, called proteases, whose action is believed to lead to Alzheimer’s disease. Memapsin 2 works with another enzyme (called gamma-secretase) to cut a longer protein called Amyloid Precursor Protein (APP). The by-product form the cut is known as beta-amyloid, or “A-beta.” A-beta then accumulates in the brain and form plaques and tangles which lead to Alzheimer’s disease.
The next step for the OMRF team was to create an inhibitor or “decoy” for memapsin 2, and this breakthrough was reported in April. Dr. Jordan Tang is world renowned for his work concerning this family of proteases, and such knowledge led to the design of a highly potent inhibitor for memapsin 2. Tang’s research efforts on the basic principles of this type of enzyme/inhibitor contributed to the speedy design of the memapsin 2 inhibitor. The enzyme and inhibitor concept for memapsin 2 is similar to the protease inhibitors which have been created to fight HIV and AIDS.
The inhibitor acts as a sticky substance, similar to a “chemical chewing gum.” Once memapsin 2 adheres to the decoy, the enzyme is essentially disabled. Thus, the enzyme causing Alzheimer’s disease is stopped before it can cut the protein, create A-beta, and make the plaques and tangles associated with the disease. The three-dimensional crystal model published in Science reveals what a culprit involved in Alzheimer’s disease looks like for the first time.
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, aging, children’s diseases and genetic disorders.
For additional information, including past press releases, news articles, or graphics, please contact Andrea Miles at 405-271-7159. The information can also be obtained from OMRF’s web site: http://www.omrf.ouhsc.edu/
For copies of the research paper, please contact the News and Information office of Science at 202-326-6440.
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