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Fig. 1 | Molecular Neurodegeneration

Fig. 1

From: Targeted degradation of ⍺-synuclein aggregates in Parkinson’s disease using the AUTOTAC technology

Fig. 1

p62 agonists induce autophagy in PD cellular models. A Western blot in HEK293A cells transduced with either h-α-syn monomers or h-α-syn PFFs (48 h). B Autophagic flux assay in HEK293A cells transduced with h-α-syn PFFs (48 h) upon co-treatment with HCQ (25 μM, 48 h). C Structures of ATL compounds. D Western blot in HeLa cells, subsequent to ATL treatments (1 μM, 24 h). E In vitro p62 aggregation assay in 293 cell lysates. ATLs were treated at final concentration of 1 mM. F and H Western blots in rat cortex primary neurons. ATLs were treated at 1 μM for 24 h. G and I Quantifications of F and H (n = 3, each). Data are presented as the mean (SEM) where relevant. P-values (from two-sided unpaired t tests): n.s. (not significant) P-value > 0.05, * P ≤ 0.05, ** P < 0.01. J Immunocytochemistry in HEK293A cells transduced with h-α-syn PFFs (48 h). The cells were then treated with ATL7 (1 μM, 24 h). K-M Quantifications of G (n = 6–7 for K and L; for M, the numbers of p62+LC3+ puncta were counted per cell in 20 cells per group). Data are presented as the mean (SEM) where relevant. P-values (from two-sided unpaired t tests): *** P < 0.001. N Western blot in HEK293A cells transduced with h-α-syn PFFs (48 h) were treated with ATLs at 1 μM for 24 h. O Immunocytochemistry in HEK293A cells transduced with h-α-syn PFFs (48 h), subsequently treated with ATL7 (1 μM, 24 h) and baf. A1 (200 nM, 6 h). P Western blot of Triton X-100 insoluble fraction in HEK293A cells. The cells were transduced with h-α-syn PFFs (48 h) followed by treatment with ATLs at 1 μM for 24 h. All the scale bars in this figure represent 10 μm

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