Figure 7.

Proteasome impairment induced the formation of pTDP-43 aggresomes in sporadic ALS/FTD fibroblasts. (A) Fibroblasts from sporadic ALS/FTD were treated for 24 h with 20 μM MG132 or vehicle control (DMSO) and then immunostained with pTDP-43 (red) and ubiquitin, HSP70, vimentin, LC3 or LAMP2 (green) antibodies. (B) Formation of pTDP-43 aggresome was microtubule-dependent. Fibroblasts from sporadic ALS/FTD were treated for 24 h with vehicle control, 20 μM MG132, or 20 μM MG132 plus 2 μg/ml nocodazole (Noco) for 24 h and were immunostained with anti-pTDP-43 (red) and anti-p62 (green) antibodies. Nuclei were visualized by DAPI stain (blue). Aggresomes were indicated by white arrows. pTDP-43 microaggregates were indicated by white arrow heads. HSP70, heat shock protein 70 kDa; LAMP2, lysosomal-associated membrane protein 2; noco, nocodazole; pTDP-43, phosphorylated TDP-43.