Interactions between iron and α-synuclein pathology in Parkinson's disease

Both iron deposition and a-synuclein aggregation are neuropathological hallmarks of Parkinson's disease (PD). We aimed to summarize the extensive interactions between these two factors. The direct structural links between iron and alpha-synuclein suggest that structural reorganization provokes alpha-synuclein conformational change. Iron post-transcriptionally regulates alpha-synuclein synthesis in the presence of iron-responsive element. Increased oxidative/nitrative stress induced by iron is believed to be involved in the post-translational modulation of asynuclein. Iron modulates proteolytic pathways and therefore participates in the regulation of alpha-synuclein levels. Meanwhile, the recycling of iron through ferritin degradation suggests a link from the aspects of the degradation signaling pathway. Finally, alpha-synuclein might regulate iron metabolism through its ferrireductase activity. A prominent role of alpha-synuclein in iron homeostasis is involved in the uptake of transferrin-Fe. These findings suggest that intracellular iron and alpha-synuclein are closely related to each other, contributing to the vulnerability of dopaminergic neurons or even to a vicious cycle of toxicity in the pathology of PD.