Novel Molecules to Tackle Toxic Amyloid-Beta Production in Alzheimer's

Project Summary

An enzyme called gamma-secretase has important biological functions. When it is not properly regulated, though, it can boost production of a toxic form of the Alzheimer's disease protein amyloid-beta. Under proper regulation, the very same enzyme can promote processing of nontoxic amyloid-beta while still executing its normal functions.

Lucía Chávez-Gutiérrez, PhD, and her team aim to examine the molecules responsible for regulating the activity of gamma-secretase. They first will capture how these molecules interact with the enzyme. Using these interactions as a template, they will design novel molecules with similar features and predicted behaviors.

With these designed molecules in hand, Dr. Chávez-Gutiérrez and her group will use molecular biology tools to assess how well the novel molecules boost production of nontoxic amyloid-beta without inhibiting the important normal functions of gamma-secretase. The work, which is the first to apply this rational, genetic-based approach to drug design in this context, is predicted to generate new candidates for drug development.