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2006 Grant - Wei
Role of Prostaglandin Receptor EP2 in Alzheimer's Disease
Guo Wei, M.D. Ph.D.
Johns Hopkins University
2006 New Investigator Research Grant
Prostaglandins are a group of hormone-like molecules that mediate a wide variety of biological activities in the human body. In the brain, some prostaglandins are believed to be protective while others may promote inflammation and injury. One of the reasons why nonsteroidal anti-inflammatory drugs may protect against Alzheimer's disease is that they prevent the production of prostaglandins.
EP2 is a receptor protein, a "docking site" on a cell, that binds to specific types of prostaglandin. Recently, scientists demonstrated that activation of this receptor may help protect neurons from beta-amyloid, a toxic protein fragment suspected of damaging neurons in Alzheimer's disease. Activation of the receptor is also believed to protect the brain against ischemia, or lack of oxygen, which happens, for example, when a person suffers from a stroke. In fact, stroke and Alzheimer's disease may be a synergistic combination that leads to increased neuronal death.
Guo Wei, M.D, Ph.D., and colleagues plan to test the relationships among stroke, Alzheimer's disease and activation of EP2. They will examine whether loss of EP2 exacerbates the effects of stroke in mice. Specifically, they will test to see if stroke leads to increases in beta-amyloid, poorer neuronal survival, or poorer cognitive abilities in animals that are missing the receptor. They will make similar assessments of mice that have been engineered to have Alzheimer-like pathology, including the accumulation of beta-amyloid. These studies may help unravel a complex interplay between the cardiovascular system, the brain and Alzheimer's disease.