NIH Research Festival
Lysosomal and mitochondrial dysfunction has been implicated in the pathogenesis of several neurodegenerative disorders, such as Alzheimer‚Äôs and Parkinson‚Äôs. Activation of the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) has been shown to correct lysosomal storage phenotype in patient cells from lysosomal storage disorders such as Niemann-Pick C1 (NPC1). Small molecules to activate TRAP1 have been shown to restore lysosomal and mitochondrial health. Using high-throughput screening, we identified and optimized hit compounds into lead compounds NCGC00351685 and NCGC00348187. Further studies need to be done to determine the target binding of small molecule agonists to TRAP1. We chose minimalist acetylene-containing diazirine derivatives to help us determine the binding site of these TRAP1 agonists to TRAP1.
Scientific Focus Area: Molecular Pharmacology
This page was last updated on Monday, September 25, 2023