News
Discovery of MK-8719, A Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies
Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer’s disease and progressive supranuclear palsy. Beginning with carbohydrate-based lead molecules, we pursued an optimization [...]
Mutant Huntingtin Disrupts the Nuclear Pore Complex
Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus [...]
The Discovery and Characterization of [18F]MK‐8553, a Novel PET Tracer for Imaging O‐GlcNAcase (OGA)
[18F]MK-8553 is a high affinity, selective OGA inhibitor with properties suitable for imaging OGA and determining central enzyme occupancy in both preclinical and clinical studies. Currently [18F]MK‐8553 is being utilized in humans as a PET [...]
Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice
The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as [...]