NCGC607 is a salicylic acid derivative and small molecule glucocerebrosidase (GCase) chaperone. A mutation in the GCase gene is found in patients with Gaucher disease and is the most common genetic risk factor for Parkinson’s disease. In induced pluripotent stem cell-derived (iPSC) macrophages from patients with Gaucher disease, NCGC607 (3 μM) restores protein levels of GCase, translocates it to the lysosome, and decreases lysosomal levels of the glycolipid glucosylceramide. In iPSC-derived cells differentiated into dopamine neurons (iDA), NCGC607 increases GCase activity and translocation to the lysosome, where it decreases glucosylceramide as well as glucosylsphingosine levels. It also rescues decreased α-synuclein levels in iDA neurons.
