Normally, the protein Tau resides on a docking site within a cell. In certain neurodegenerative diseases, including Frontotemporal Dementia and Alzheimer's disease, genetic and cellular mechanisms modify Tau, dislodging it from its docking site. Over time, Tau accumulates into toxic aggregates, dense protein clusters that cells cannot remove. As this waste builds up, a normally functioning nerve cell (neuron) is transformed into a defective one, and eventually the neuron dies. Studying neurons in both cell cultures and mouse models that had a mutant version of Tau, we have found that a protein called Hsp90 maintained the diseased Tau, allowing it to aggregate and kill the neuron. Inhibiting Hsp90 with small molecule discovered by our laboratory, depleted the neuron of the diseased Tau and restored normal neuron functioning. We have received funds last year from ISOA/ADDF to improve the drug-like qualities of this small molecule. Through medicinal chemistry we have made several improved versions of this agent. As a next step in their development as a drug, these small molecules need to be now evaluated for their in vivo profile, in particular we need to investigate whether they can be given as an oral pill, whether they can efficiently cross into the brain and reduce diseased Tau without being toxic. The ultimate goal of our efforts is to develop an Hsp90 inhibitor drug with human use.