Mutant alpha-synuclein and autophagy in PC12 cells

Several studies have demonstrated that overexpression of mutant alpha-synuclein in PC12 cells is related to occurrence of autophagy. The present study established mutant alpha-synuclein (A30P) -transfected PC12 cells and treated them with the autophagy inducer rapamycin and autophagy inhibitor wortmannin, respectively. Results demonstrated that mutant alpha-synuclein resulted in cell death via autophagy and involved alpha-synuclein accumulation, membrane lipid oxidation, and loss of plasma membrane integrity. Mutant alpha-synuclein (A30P) also mediated toxicity of 1-methyl-4-phenylpyridinium ion. Moreover, rapamycin inhibited alpha-synuclein aggregation, while wortmannin promoted alpha-synuclein aggregation and cell death. To further determine the role of autophagy due to mutant alpha-synuclein, the present study measured expression of microtubule-associated protein light chain 3. Results revealed that wortmannin and 1-methyl-4-phenylpyridinium ion inhibited expression of microtubule-associated protein light chain 3, while rapamycin promoted its expression. These findings suggested that abnormal aggregation of alpha-synuclein induced autophagic programmed cell death in PC12 cells.