Fig. 7: Compound 2 interacts with α-Synuclein in situ and modifies its toxicity. | npj Parkinson's Disease

Fig. 7: Compound 2 interacts with α-Synuclein in situ and modifies its toxicity.

From: An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ

Fig. 7

A Volcano plot shows proteins with structural changes detected by LiP-MS upon addition of compound 2 to a lysate of α-Synuclein PFF-seeded primary rat neurons. Note that the changing α-Synuclein peptide is specific for rat α-Synuclein and can therefore be confidently assigned to the endogenous neuronal protein and not to the added seeds. B Mapping structurally altered α-Synuclein peptide onto the sequence of α-Synuclein upon addition of compound 2 to a lysate. C GO enrichment analysis for all significant hits in (A). D Volcano plot showing LiP-MS hits structurally altered in primary rat neurons seeded with α-Synuclein and treated with compound 2, compared to untreated cells. The α-Synuclein and tau hits are marked; 61–67 indicates the location of the α-Synuclein peptide that is altered; note that this peptide cannot distinguish between rat and human α-Synuclein. E Mapping structurally altered peptide onto the sequence of α-Synuclein upon treating α-Synuclein seeded live rat neurons with compound 2. F GO enrichment analysis of LiP-MS hits in (D). Relative number of neurons (G) or TH positive neurons (H), relative neurite length of TH positive neurons (I) and relative alpha-synuclein quantity (J) upon treatment of neurons with PFFs and different concentrations of compound 2.

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