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Figure 3 | Orphanet Journal of Rare Diseases

Figure 3

From: Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy

Figure 3

BCL, NTX, SRB and their mix (PXT3003) down-regulate Pmp22 mRNA expression in RT4 Schwannoma cells. (A) After a treatment of 8 hours of RT4 Schwannoma cells with single compounds (100 nM of BCL, 100 nM of NTX or 10 μM of SRB) and with PXT3003 combination (100 nM of BCL, 100 nM of NTX and 10 μM of SRB; same drug ratio that was used for all doses in DRG co-cultures), a significant decrease of Pmp22 mRNA expression level was observed when compared to vehicle (Actb and Rps9 used together as reference genes) with a significant observed higher efficacy of PXT3003 over single compounds. (B) The same drugs had no effect on Mpz expression (Actb and Rps9 used as reference genes). (C) The expression of Pmp22 with respect to Mpz was significantly decreased after PXT3003 treatment, unlike single compounds. Three different experiments using 2 cultures each with 3 replicates were performed and analysed. *P < 0.05, ***P < 0.001 vs Vehicle; ANOVA with Dunnett’s test. #P < 0.05 vs the most active compound; post-hoc contrast test. Data are shown as mean + SEM.

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