Within previously ADDF-funded study, we have characterized novel modulator of mitochondrial function, a tricyclic pyrone compound CP2. Administration of CP2 significantly delayed the onset and development of cognitive and behavior phenotype in three transgenic animal models of familial Alzheimer's Disease (FAD). However, since the intellectual property on CP2 will mature in a few years, there is a concern that it will be difficult to attract pharmaceutical companies to invest in bringing CP2 to the clinical trials. To overcome this, we established collaboration with Nanosyn, Inc., a biotech research company that is a leading expert in the field of drug discovery and drug development. To date, we sucessfully accomplished the proposed goals and generated patentable new molecular entities that mimic CP2 action in vitro and in vivo (patent pending). Four classes of hit compounds with properties superior to CP2 were identified and selected for future studies/optimization. Further, we identified molecular mechanism of CP2 action, which helped to increase the in vitro and in vivo assays to screen for the CP2-like compounds. This project was funded by ADDF since 2011. Based on our progress, we would like to request a renewal of this grant for additional year to continue preclinical lead optimization. The work will be conducted in collaboration with Nanosyn, Inc; the outcomes will allow to complete preclinical optimization of the lead compound in order to identify a preclinical candidate.