PARP1 and Huntington disease: It is also possible that PARP1 inhibition was beneficial in mice (and would in fact be beneficial in HD patients), if the “treadmilling” activity of PARP1,92 by which PARP1 hydrolyzes NAD+ to generate free ADP-ribose, is responsible for the reduced PAR levels that we observed.65 Alternatively, the results could be explained by yet another mechanism, as is the case in a mouse model of spinal and bulbar muscular atrophy (SBMA), which benefited from olaparib treatment, despite having lower levels of PAR in quadricep tissue, via restoration of hexokinase activity and glycolysis.93