24. An Alzheimer’s Preventive Enzyme
Linda Nicholson
Linda K. Nicholson, Molecular Biology and Genetics, and her colleagues discovered that an enzyme, Pin 1, previously known to prevent the dementia of Alzheimer’s disease now appears to be pivotal in guarding against Alzheimer’s itself. Scientists knew that Pin 1 could prevent the tangles of knotlike brain lesions associated with Alzheimer’s, but Pin 1 also seems to help prevent the buildup of plaque or flat deposits on the surface of brain cells. This new finding provides a specific molecular interaction that can be used as a target in drug discovery. Using nuclear magnetic resonance, the researchers observed Pin 1 acting on a protein called amyloid precursor protein (APP), which scientists believe to be the primary cause of Alzheimer’s. When APP gets a phosphate group attached to its tail, it toggles slowly back and forth between two forms: one form leads to buildup of plaque and disease, while the other form is part of normal function and helps neurons grow and survive. Pin 1 acts as a molecular accelerator, allowing APP to toggle back and forth between its bad and good forms 1,000 times faster than if Pin 1 were not present. Without Pin 1, the disease-causing form of APP has a chance to build up to high levels toxic to cells, leading to plaque lesion. The research will be a foundation for new therapeutic approaches to treating Alzheimer’s.