Loss of PA28αβ capped proteasomes during HD progression.

Native PAGE showing proteasome activity labeling and PA28α immunoblot for different brain regions of Hdh Q150 (A) and R6/2 (B) during disease progression. The upper blots depict fluorescent ABP signal, only showing the bands representing PA28 capped proteasomes. The graphs in the lower panels show quantification of the fraction of capped PA28αβ (PA28α bound to 20S, black arrowheads, divided by the total pool of PA28α (black and open arrowheads). Data are shown as mean ± SEM ( Hdh Q150 n = 3/4; R6/2 n = 3/4). A one sample t-test is performed after normalization to the WT animal of the same age-group (p-values are only given for the latest age group). One sample t-test; Hdh Q150 22m cortex p = 0.0006; striatum p = 0.0269; hippocampus p = 0.0119; cerebellum p = 0.8258; brain stem p = 0.3801; R6/2 14wk cortex p = 0.1620; striatum p = 0.0546; hippocampus p = 0.0052; cerebellum p = 0.5529; brain stem p = 0.4152. * indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001. WT = wildtype; KI = knock-in; TG = transgene; m = months; wk = weeks.