IP3R-Presenilin Interaction: Calcium Dysregulation in AD
This study is designed to test how presenilin interacts with calcium signaling proteins, resulting in changes to the presenilin function. The study will also examine how altered calcium signaling in turn affects other cell functions. These studies should provide new insights into the molecular mechanisms of AD and into the development of novel targets for therapeutic interventions.
Alzheimer's disease (AD) is a common form of dementia involving slowly developing degeneration of neurons in the brain. The causes of AD are still not clear, but mutations in some proteins that result in early-onset cases of the disease provide clues. One of these proteins, presenilin, causes the amount of calcium in cells to be abnormally regulated. Because calcium regulates many brain functions, this abnormality may be a key part of the disease. We have discovered a mechanism whereby mutant forms of presenilin that cause AD alter the function of an important protein that regulates calcium signals in cells. Calcium in cells is precisely regulated, because it is toxic if its concentration is too high. Chronic abnormal calcium regulation as a result of mutations in presenilin may therefore cause cellular toxicity that leads to cell death. We plan to study how presenilin interacts with this important calcium signaling protein to alter its function, and how altered calcium signaling in turn affects cell functions. These studies should provide new insights into the molecular mechanisms of AD and into the development of novel targets for therapeutic interventions.