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2011 Grants - Wang
Presenilin 1 as a Regulator of Mitochondrial Dynamics
Xinglong Wang, Ph.D.
Case Western Reserve University School of Medicine
2011 New Investigator Research Grant
Brain cells contain structures called mitochondria that perform many important tasks, such as using oxygen and nutrients to provide energy for the cells. In Alzheimer's disease, however, mitochondria lose their ability to function normally. Yet the mechanisms behind this loss of function are unknown.
In preliminary studies with cultured brain cells, Xinglong Wang, Ph.D., and colleagues found that mitochondria divide and combine abnormally in the Alzheimer's brain. They also found that these abnormalities may involve mutant genes for the protein presenilin 1. The normal presenilin 1 gene (PS1) produces a protein with beneficial effects on mitochondria. But mutant PS1 —a genetic suspect in the early-onset, inherited form of Alzheimer's — produces a protein that can alter how mitochondria function and how they are transported within cells. Dr. Wang's research group further observed that normal PS1 interacts with dynamin-like protein 1 (DLP1), a protein known to promote normal mitochondrial division and transportation. This finding suggests that mutant PS1 may cause its mitochondrial damage by altering the functions of DLP1.
For this grant, the researchers will conduct a larger study to confirm and extend their earlier results. They will continue to examine the adverse effects of mutant PS1 on mitochondria and how these effects may lead to brain cells' dysfunction. The team will also search for mechanisms underlying mutant PS1's role in mitochondrial damage. Results of this studycould reveal new information about the genetic causes of Alzheimer's.