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, untreated or treated with epoxomicin for 24 hours, were assessed for SDSsoluble pS129 ?-Syn. F. Cells were harvested and subjected to fractionated western immunoblotting (Tx-100 and SDS soluble fraction) with anti-pS129, anti-cjun, and anti-?-tubulin antibodies. G, H. Quantification of SDS-soluble phosphorylated ?-Syn levels (monomeric species) in d7 (G) and 7d-/2d+ (H) cells. For quantification (B, G and H), data are presented as the mean ± SD of 3 independent cell preparations; one-way ANOVA with Bonferonni's correction was used for (B) and student's t-test for (G) and (H). I. 7 days after high-dose PFF (400ng/ml) addition, -and +DOX cells, non-treated, epoxomicin-or bafilomycin-treated, were lysed, fractionated and subjected to PK treatment, followed by western immunoblotting with anti-pS129, anti-p62, anti-LC3 and anti-?-tubulin antibodies. Representative blot from 3 independent cell preparations. J,K. -, + DOX and 7d-/2d+ cells (without or with high-dose PFFs-400ng/ml), in the absence or presence of pharmacological reagents (bafilomycin, epoxomicin) were lysed at indicated time points (day 7, day 9) with a nuclear-sparing buffer, Syn (red) and Tuj1 (green) was observed using fluorescence confocal microscopy. Scale bar 30 ?m. E. 7 and 9 days after high-dose PFF (400ng/ml) addition, differentiated SH-SY5Y cells (-or +DOX and 7d-/2d+)

, SH-SY5Y differentiated cells with inducible expression of ?-Syn can serve as a model to investigate aggregation propensity and clearance of PFFtriggered ?-Syn assemblies. PFFs are internalized within 48h (1) and 6 days post-PFF, endogenous ?-Syn is seeded and detected mostly around the nucleus (2), Figure 7. Schematic illustration of the SH-SY5Y inducible neuronal model, fine-tuned for investigating aggregated ?-Syn turnover