We propose to identify the molecular mechanisms and test the efficacy of two members of tricyclic pyrone (TP) family, CP2 and TP70, which were shown to efficiently block amyloid beta oligomerization. Both molecules penetrate blood brain barrier and demonstrate high bioavailability. Short- and long-term CP2 treatment delayed the onset and slowed down the progression of Alzheimer's Disease (AD) in multiple mouse models of familial AD (FAD). CP2 treatment prevented memory loss in FAD mice and restored mitochondrial dynamics and function and brain energetics in vitro and in vivo. CP2 treatment did not affect animal development, ability to breed, and did not cause measurable side effects. Our preliminary data suggest CP2 is a promising drug that could be beneficial to revert early AD pathology. We propose to identify the mechanism of mitochondrial protection in neurons by CP2 and TP70. We aim to determine whether these molecules are only efficient against amyloid beta peptides or possess general ability to protect mitochondria from multiple toxins. Our experiments will elucidate the mechanism of CP2 and TP70 action and provide a rationale for clinical studies in humans.