Fig. 5: Linking acetylated α-Tubulin redistribution with α-Synuclein aggregation in Lewy body formation.

a Six different stages are distinguishable in post-mortem human brain sections of PD patients following PLA assay for detecting α-Synuclein oligomers (green) and immunofluorescence for detecting acetylated α-Tubulin (red). b Schematic model showing the hypothetical sequences of events in LB formation starting from the redistribution of acetylated α-Tubulin (red) in the cell bodies of dopaminergic neurons to α-Synuclein oligomers (green) and Ser129 P α-Synuclein (yellow in the squared insets, see supplementary Fig. 6). Stage 1 shows the strong presence of acetylated α-Tubulin accumulated in the soma of neurons; in stage 2, acetylated α-Tubulin is still accumulated inside the cell body while some small and spared α-Synuclein oligomers and Ser129 P α-Synuclein appear; in stage 3, acetylated α-Tubulin starts to accumulate into a small aggregate with α-Synuclein oligomers and also Ser129 P α-Synuclein; stage 4 shows acetylated α-Tubulin in a bigger and compact aggregate with an undefined shape with α-Synuclein oligomers inside and strong Ser129 P α-Synuclein signal, whereas the cytoplasm is now negative for acetylated α-Tubulin staining; stage 5 shows a ring-shaped aggregate where acetylated α-Tubulin forms an external ring and α-Synuclein oligomers are distributed not only along the ring but also inside it. Ser129 P α-Synuclein has a pattern of distribution similar to α-Synuclein oligomers; in stage 6, the ring-shaped aggregate is weakly positive for acetylated α-Tubulin and has few α-Synuclein oligomers, while the Ser129 P α-Synuclein fibrils are still abundant in the external part. Hoechst staining (blue) is detectable in the core of aggregates at stage 6. Scale bar, 20 μm.