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2008 Grants - Yoon
The Role of JNK3 in APP Trafficking
Sungok Yoon, Ph.D.
Ohio State University Research Foundation
2008 Investigator-Initiated Research Grant
Amyloid precursor protein (APP) is a key protein in the development of Alzheimer pathology. It is cut to yield beta-amyloid, a fragment of APP that aggregates to form amyloid plaque, a characteristic feature of Alzheimer pathology. Before it is cut, however, APP is transported to specific regions within nerve cells. Such trafficking of APP is crucial to the proper function of the cells.
Sungok Yoon, Ph.D., and colleagues are studying how the trafficking of APP is altered in nerve cells affected by Alzheimer's disease. They have focused on a protein known as c-jun-N-terminal kinase-3 (JNK3), which is increased in nerve cells that are damaged, such as in Alzheimer's disease. The researchers have found evidence that activation of JNK3 interferes with the trafficking of APP, possibly contributing to abnormal accumulation of APP.
For their experiments, Dr. Yoon and colleagues use a model system of isolated nerve fibers, which enables them to study how proteins such as APP are transported. The researchers plan to study how JNK3 affects the trafficking of APP in mice that have been genetically altered to express Alzheimer-like pathology. In addition, some Alzheimer-like mice have been further genetically altered to prevent expression of JNK3. Dr. Yoon's group plans to study how APP is transported in nerve cells from these animals.
These experiments will enable the researchers to test whether JNK3 is involved in the production of beta-amyloid in Alzheimer's disease, and they may help determine whether JNK3 is a suitable target for drugs to slow or halt the progression of Alzheimer's disease.