Cytotoxic sCAGs are increased in brain regions of HD.

<p>A. sCAG levels are increased in affected brain areas from R6/2 HD mouse model compared to control mice. sCAG were quantified by qRT-PCR using RNU6B as the reference sRNA; HC, hippocampus; STR, striatum cortex; CX, cortex; and CB, cerebellum. Values represent mean fold change with respect the control samples ± SEM (n = 3; *p<0.05 ***p<0.001). B. Increased expression of sCAG in HD human brain samples compared to control subjects. CA, caudate; and FC, frontal cortex. RNU66 sRNA was used as reference sRNA. Values represent mean fold change with respect to the control samples ± SEM (n = 3; *p<0.05 ***p<0.001). C. HD-derived sRNA pools induce neuronal toxicity. sRNA pools were isolated from control and HD human brain samples and delivered to differentiated SH-SY5Y cells; cell death was determined 24 hours later. The use of anti-sCAG dramatically reduced the cytotoxic effect. Control sRNA inhibitors (scrambled anti-sRNA) were used as a negative control. Values represent mean of the ratio (HD sRNA toxicity/Control sRNA toxicity) for each condition ± SEM (experiments were performed in quintuplicates, n = 6; *p<0.05). Pools from four control individuals and four patients with HD were used.