Fig. 3.

Relationships among ferroptosis, apoptosis, and autophagic death in PD. Accumulation of iron and misfolded α-syn in SNpc dopaminergic neurons are the hallmark of PD. Although unfolded or misfolded α-syn is partially degraded by the autophagy pathway, its overexpression can result in autophagic death. At the mitochondrial level, α-syn and ROS accumulation induce mitochondrial damage and fragmentation. The increase in the number of damaged mitochondria can trigger apoptosis through the release of Cyt C, degradation of the anti-apoptotic Bcl-2 family, and activation of Bax. In the presence of Fe²⁺, the most harmful highly-reactive hydroxyl radical is produced by the Fenton reaction, causes oxidative stress, and then triggers ferroptosis. α-syn, α-synuclein; Apaf-1, apoptotic protease activating factor 1; Bak, Bcl-2 homologs antagonist/killer; Bax, Bcl-2-associated X protein; Bcl-2, B cell lymphoma-2; Cyt C, cytochrome C; ROS, reactive oxygen species