Proteasome Inhibition in Alzheimer's Disease

Jeffrey Keller, PhD
University of Kentucky (Lexington, KY)
Year Awarded:
Grant Duration:
April 1, 2000 to March 31, 2002
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Southeastern

Proteasome Inhibition in Alzheimer's Disease


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.


Ding, Q. and Keller, J.N. (2001) Proteasome inhibition in oxidative stress neurotoxicity: implications for heat shock proteins. J. Neurochem. 77(4):1010-1017.  

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