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Reducing presenilin 1 expression counteracts the cytotoxicity of full-length Ryk overexpression in mutant htt striatal cells.

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posted on 2014-06-24, 03:20 authored by Cendrine Tourette, Francesca Farina, Rafael P. Vazquez-Manrique, Anne-Marie Orfila, Jessica Voisin, Sonia Hernandez, Nicolas Offner, J. Alex Parker, Sophie Menet, Jinho Kim, Jungmok Lyu, Si Ho Choi, Kerry Cormier, Christina K. Edgerly, Olivia L. Bordiuk, Karen Smith, Anne Louise, Michael Halford, Steven Stacker, Jean-Philippe Vert, Robert J. Ferrante, Wange Lu, Christian Neri

Assays were performed using caspase 3/7 activity in cells subjected to serum deprivation. (A) PS1 and PS2 siRNA treatment enhances the viability of mutant htt striatal cells. Data are mean ± SD (n = 3), *p<0.01 compared to scramble RNA. Significance was tested using one-way ANOVA, with correction for multiple testing by Tukey's Multiple Comparison Test. (B) Representative Western blots showing decreased levels of PS1/PS2. (C) Knockdown of PS1 reduces the cytotoxic effects of overexpressing full-length Ryk in mutant htt striatal cells, with no effect detected on the cytotoxic effects of overexpressing Ryk-ICD. Data are mean ± SD (n = 4), *p<0.05 and **p<0.01 compared to scramble RNA. Significance was tested using one-way ANOVA, with correction for multiple testing by Tukey's Multiple Comparison Test. EV, empty vector; ns, not significant. (D) Representative Western blots showing decreased levels of PS1 and expression of Myc-tagged Ryk species and Myc-tagged Ryk-ICD. *Nonspecific signal.

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