Chen, Wen, Jiang, Wang, Song, Xie (2019) Interactions between iron and α-synuclein pathology in Parkinson's disease Free radical biology & medicine 141() 253-260


Both iron deposition and α-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 α-synuclein suggest that structural reorganization provokes α-synuclein conformational change. Iron post-transcriptionally regulates α-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 α-synuclein. Iron modulates proteolytic pathways and therefore participates in the regulation of α-synuclein levels. Meanwhile, the recycling of iron through ferritin degradation suggests a link from the aspects of the degradation signaling pathway. Finally, α-synuclein might regulate iron metabolism through its ferrireductase activity. A prominent role of α-synuclein in iron homeostasis is involved in the uptake of transferrin-Fe. These findings suggest that intracellular iron and α-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. Copyright © 2019 Elsevier Inc. All rights reserved.