To view an abstract, select an author from the vertical list on the left.
2012 Grants - Kukar
The Role of Progranulin in Alzheimer's Disease
Thomas Kukar, Ph.D.,
2012 New Investigator Research Grant
The brain protein progranulin (a cell-derived growth factor) is produced by a gene known as granulin. Variations in the granulin gene have been associated with many cases of frontal lobar degeneration, a major neurological disorder. Granulin mutation may also be a risk factor for Alzheimer's disease, making progranulin a potential target for Alzheimer's drug therapies. Yet the development of such drugs has been hindered because little is known about progranulin's function in the brain.
Thomas Kukar, Ph.D., and colleagues hypothesize that progranulin is a type of "neurotrophic growth factor," a protein that the body uses to support brain cell health and survival. Specifically, progranulin likely helps bolster the cells' ability to communicate with one another. Granulin resulting from mutation, however, may produce proteins that lack the ability to carry out their normal activities. The presence of dysfunctional progranulin may make cells more vulnerable to degeneration and death in Alzheimer's disease.
For this proposed study, Dr. Kukar and colleagues will further elucidate the functions of progranulin in the brain. They will examine mice engineered to express the human form of the protein, searching for patterns of progranulin activity throughout the animals' brains. They will then compare these patterns to those found in autopsied human brain tissue—so as to determine how progranulin activity may become altered in old age or disease. The team will also conduct experiments with cultured cells to determine the molecular mechanisms underlying progranulin function. For example, they will determine how and where progranulin interacts and binds to cells. Finally, the team will identify possible therapeutic approaches for moderating the loss of progranulin activity.