Restoring Proteasome Function in Neurodegenerative Disease

The objective in this proposal is to determine if our proteasome-activating peptides can be targeted to specific cells (i.e. neurons) using antibody-fusion approaches and to generate a mouse model to robustly test the consequences of proteasomal upregulation in neurons.

To achieve our objective, we propose the following aims:

1. Designing strategies to deliver HbYX-motif containing peptides into selected cells to activate the proteasome and
2. Determine if proteasome activation by genetic mutations can ameliorate the pathogenesis of Alzheimer’s in cellular disease models.