Proteasome Inhibition in Alzheimer's Disease

Project Summary

Although it is clear that increased oxidative damage occurs in AD-affected brains, the mechanism(s) responsible for increasing oxidative stress is still unknown. Dr. Keller has recently found that the formation of a specialized assembly of enzymes known as the multicatalytic proteasome (MCP) is inhibited in AD brains, and that this inhibition leads to oxidative damage and neuron death. Because the MCP is normally involved in breaking down and recycling proteins, it serves important cellular functions. Dr. Keller is focusing on testing the hypothesis that oxidative stress causes inhibition of the MCP, and that MCP inhibition causes the accumulation of oxidized protein and damaged DNA.