Autophagy is the major intracellular catabolic mechanism by which cytoplasmic materials can be degraded in the lysosome.Although physiological levels of autophagy are essential for normal cellular homeostasis, either absence of autophagy or excessive autophagy may lead to cell death.Recent studies including ones from our laboratory revealed that oxidative stress,mitochondrial dysfunction, and accumulation of misfolded proteins are implicated in dopaminergic neurodegeneration.Previously, we reported that prototypic dopaminergic neurotoxin, MPP+-induced dopaminergic neuronal cell death accompanying with the features typical of autophagy along with impairment of autophagic.In continuation of our previous study,we specifically asked whether and how 6-hydroxydopamine (6-OHDA) causes autophagy and this phenomenon contributes to drug-induced cell death.We found that autophagic events were observed following 6-OHDA treatment in MN9D dopaminergic neuronal cell as determined by an increased in such autophagosomal marker (LC3-Ⅱ level and LC3 punctate), as well as ultrastructural alterations.In contrast to MPP+-treated cells, these phenomena were primarily caused by induction of autophagic flux.Either in MN9D cells co-treated with 3-methyladenine or in MEF cells depleted of ATG5 or ATG7 partially inhibited 6-OHDA-induced cell death,indicating that excessive autophagic induction may significantly contribute to 6-OHDA-inducedc cell death.Since 6-OHDA-induced cell death is demonstrated to be ROS-induced and caspase-dependent, in a separate study, we further attempted to investigate whether antioxidant or caspase inhibitor may regulate 6-OHDA-induced autophagic flux.Outcomes of these studies will be presented at the meeting.