Cells have been found to die via controlled mechanisms in response to various stimuli and this Programmed Cell Death (PCD) is an essential function to maintain the health of the organism. One well-known mechanism of cell death, apoptosis, occurs with little consequence to the surrounding cells, however a different form of PCD, necrosis, results in the release of inflammatory substances from the cell which can, in turn, induce necrosis in surrounding cells. Notably, both of these pathways are under the influence of the mitochondria within the cell, and in particular by the activation state of a pore, or channel, that forms at the surface of the mitochondrial membrane known as the Mitochondrial Permeability Transition Pore (MPTP). One of the stimuli that have been found to activate the MPTP is amyloid beta (A) and it has been shown that A can be toxic to neurons via activation of the MPTP. The well-established connection between A and Alzheimer's disease (AD) raises the question of whether prevention of MPTP activation could protect neurons from the effects of this protein and slow the progression of AD. Cyclophilin D (CypD) is an essential component of the MPTP complex and deletion of CypD was shown to have a protective effect on neurons. Cypralis has discovered new classes of cyclophilin inhibitors, some of which inhibit CypD and are protective towards cells, and others that are able to penetrate the brain but are not selective enough to be evaluated in animal models of AD. Cypralis proposes to apply its medicinal chemistry expertise, along with its biological assays, to make brain penetrating compounds that are selective for CypD to be used to validate this exciting target in neurodegeneration.