Scientists also want to determine whether mutations in the gene that codes for the Pin1 enzyme play a role in Alzheimer’s. While the disease has a genetic component, scientists have identified genetic defects in only about five percent of Alzheimer’s cases. The other 95 percent may have a series of genetic missteps that each exert a small effect and add up to an increased risk of the disease.
Tanzi is now trying to determine if Pin1 is such a candidate by searching for mutations in the Pin1 gene in a large group of families affected by Alzheimer’s. He says that preliminary results point to a genetic defect in the same area as this gene. Lu and others are also trying to determine whether reduced Pin1 levels in the blood can be used as a marker for increased risk of Alzheimer’s.
Lu’s team is also searching for small molecules that can turn up or down the Pin1 enzyme’s activity. However, the enzyme may prove to be a difficult drug target: it’s involved in many cellular functions, so drugs acting on it would need to be carefully monitored for unwanted effects.
The Pin1 enzyme also plays a role in cancer, which has been the major focus of Lu’s work. In cancer, though, its role is reversed: while decreasing Pin1 activity in animal models leads to signs of Alzheimer’s, cancer is linked to an overexpression of the Pin1 enzyme. Those converse effects could complicate the hunt for a drug that targets the enzyme.