Mitochondria is a critical target for neuroprotection that regulates neuroinflammation and subsequence neurodegeneration, a process exacerbated by melatonin deficiency. The rate limiting enzymatic step in melatonin synthesis is performed by aralkylamine N-acetyltransferase (AANAT), found in the mitochondrial matrix. Knockout of AANAT in neuroblastoma cells (AANAT-KO N2a) cause defective melatonin synthesis and synaptic vulnerability. These cells can thus be used as a model of aging and synaptic pruning. The major goal is to optimize and scale an in vitro screening assay for synaptic loss to identify compounds that will preserve functional synapses in a neuronal cell line that is deficient in melatonin production. This project is a collaboration with Robert Friedlander, MD, Chair of the Department of Neurosurgery, funded through the Immune Transplant & Therapy Center (ITTC).