Figure 9. Schematic diagram of the lysosomal effects and relevant cell death pathways induced by aberrant ASYN.

Aberrant ASYN induces in all settings CMA dysfunction. When this leads to compensatory macroautophagy induction (as assessed by autophagosome formation/accumulation), autophagic cell death, inhibited by macroautophagy inhibitors, occurs. In certain settings (A53T ASYN in neuronally differentiated SH-SY5Y cells), lysosomal dysfunction occurs independent of CMA targeting and may contribute to death (dotted arrows).