This protein may be overexpressed in brains of individuals with Alzheimer's disease. Our focus is on the function of this protein and preliminary results indicate it has RNase activity. The expression of iron regulatory proteins in cells has received a high level of interest in cell and molecular biology as a model for translational regulation. The possibility that these proteins may also have RNase activity is novel and exciting. In relation to the second area, cellular iron management, we have focused on the expression of ferritin subunits.
Ferritin is made of different ratios of two subunits and the subunits are functionally distinct.
We are investigating the response of these two subunits to age and disease and the relationship of their response to oxidative damage. We know that H ferritin does not increase in sufficient amounts in Alzheimer's and Parkinson's disease to keep pace with iron accumulation. Finally, because of our observations that iron accumulates around neuritic plaques with amyloid cores in Alzheimer's Disease and a segment on the amyloid gene responds to altered iron levels in cells we are addressing the relationship between overproduction of amyloid that kills cells in the brain and ultimately causes Alzheimer's Disease. In general, our work addresses fundamental questions of cell and molecular regulatory mechanisms as iron is an essential nutrient but if unregulated becomes a potent toxin. The technical approaches we use involve in vitro and in vivo systems including mouse lines in which protein expression has been genetically manipulated.