The study investigates the degradation pathways of α-synuclein, a protein implicated in Parkinson's disease (PD). Using a stable inducible PC12 cell model, the researchers found that α-synuclein is degraded by both the proteasome and autophagy. Proteasome inhibitors increased α-synuclein levels, while autophagy inhibitors and the autophagy inducer rapamycin decreased α-synuclein levels. Electron microscopy revealed α-synuclein in organelles with autophagic morphology, supporting the role of autophagy in its degradation. The findings suggest that rapamycin, a potential autophagy inducer, could be a therapeutic target for PD, as it is designed for long-term use in humans.The study investigates the degradation pathways of α-synuclein, a protein implicated in Parkinson's disease (PD). Using a stable inducible PC12 cell model, the researchers found that α-synuclein is degraded by both the proteasome and autophagy. Proteasome inhibitors increased α-synuclein levels, while autophagy inhibitors and the autophagy inducer rapamycin decreased α-synuclein levels. Electron microscopy revealed α-synuclein in organelles with autophagic morphology, supporting the role of autophagy in its degradation. The findings suggest that rapamycin, a potential autophagy inducer, could be a therapeutic target for PD, as it is designed for long-term use in humans.