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2014 Grants - Wang
The Role of DLP1 Phosphorylation in Alzheimer’s Disease
Xinglong Wang, Ph.D.
Case Western Reserve University
2014 New Investigator Research Grant
All cells, including brain cells contain structures called mitochondria that perform many important tasks, such as using oxygen and nutrients to provide energy for cells. In early Alzheimer's disease, however, mitochondria lose their ability to function normally. However, the mechanisms behind this loss of function are unknown.
Xinglong Wang, Ph.D., and colleagues have been studying the role of mitochondria in Alzheimer’s using (1) brain tissue from people who had Alzheimer’s disease and (2) mice engineered to develop Alzheimer’s-like brain changes. The researchers found that mitochondria divide and combine abnormally in the Alzheimer's brain. They also found that these abnormalities may be linked to a protein called dynamin-like protein 1 (DLP1), which is used to promote healthy mitochondrial division and transportation. DLP1 is normally regulated by a chemical process called phosphorylation where phosphate groups are added. This process becomes altered in Alzheimer’s disease, possibly limiting the ability of DLP1 to maintain mitochondrial function and protect brain cell health.
Dr. Wang and colleagues hope to determine how chemically altered DLP1 may change or damage mitochondria in Alzheimer’s disease. They will also determine whether promoting healthy modification of DLP1 can help prevent mitochondria-related brain cell loss. To conduct these experiments, the team will use brain cells grown in a dish and Alzheimer’s-like animal models. The results of Dr. Wang’s study could shed new light on how early Alzheimer’s disease progresses, and suggest new potential targets for treating Alzheimer’s disease.