Summary

Our data will provide direct evidence of the relationship between mitochondrial trafficking, function and memory. Data will validate the axonal trafficking of mitochondria as a therapeutic target; reveal the mechanism of HDAC1 toxicity in the pathogenesis of AD and provide the mechanistic explanation for therapeutic role of HDAC inhibitors.

Project Details

Histone deacetylase 1 (HDAC1) is a protein that controls gene activity. Problems with HDAC1 can both disrupt the activities of other genes, and can promote cell death by disrupting movement of the mitochondria, the cell's “energy powerhouses.” Dr. Eugenia Trushina, Dr. Joseph Poduslo, and colleagues will look for what specifically causes the problem with mitochondrial movement. In particular, they'll look at the effect of beta‐amyloid proteins on mitochondrial motility in cultured cells and in brain slices from mice with Alzheimer's. Once they pinpoint the mechanism of dysfunction, the next step would be to create and test drugs that restore the mitochondrial transport and, hopefully, prevent progression of the disease.