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. 2018 May 30;27(16):2863–2873. doi: 10.1093/hmg/ddy200

Figure 4.

Figure 4.

 Inhibition of PAK signaling reduces ATXN1 levels in cells and mice. (A) Treatment of mouse primary cerebellar neuron culture with FRAX486 (PAK1/2/3i), an inhibitor of Group I PAKs, results in a decrease of pPak1 (S144) and Atxn1 levels in a concentration-dependent manner (n = 3, one-way ANOVA, **P < 0.01, ****P < 0.0001. Error bars denote SEM). (B) PF03758309, panPAK inhibitor (panPAKi), modulates Atxn1 levels in a concentration-dependent manner in mouse cerebellar neuron culture (n = 3, one-way ANOVA, ***P < 0.001, ****P < 0.0001. Error bars denote the SEM). (C) Combinatorial delivery of MEK (PD0325901, MEKi) and panPAK (PF03758309, panPAKi) inhibitors in mRFP-ATXN1 [82Q]-IRES-YFP Daoy cell line additively reduces mRFP-ATXN1 [82Q] levels (n = 3, one-way ANOVA, *P < 0.05, ****P < 0.0001. Error bars denote the SEM). (D) Intraperitoneal administration of 15 mg/kg panPAK inhibitor every 8 h for 5 days in Atxn1154Q/2Q mice reduce expanded Atxn1 [154Q] as wells as wild type, Atxn1 [2Q] levels in the cerebellum (n = 4, two-way ANOVA, **P < 0.01. Error bars denote the SEM).