Iron Dysregulation in Parkinson’s Disease: Focused on the Autophagy–Lysosome Pathway

• Published in: ACS chemical neuroscience Vol. 10; no. 2; pp. 863 - 871
• Main Authors: Chen, Lei-Lei, Huang, Yu-Jv, Cui, Jun-tao, Song, Ning, Xie, Junxia
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-02-2019
• Subjects: Animals; Autophagy - physiology; Humans; Iron - blood; Iron Chelating Agents - pharmacology; Iron Chelating Agents - therapeutic use; Lysosomes - metabolism; Parkinson Disease - blood; Parkinson Disease - diagnosis; Parkinson Disease - drug therapy; Signal Transduction - physiology; autophagy−lysosome pathway; iron; transferrin receptor; ferritin; Parkinson’s disease; α-synuclein
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.8b00390

Parkinson’s disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy–lysosome pathway contribute to the pathological development of PD, the connection between these two causes is poorly documented. The autophagy–lysosome pathway not only responds to regulation by iron chelators and channels but also participates in cellular iron recycling through the degradation of ferritin and other iron-containing components. Previously, ferritin has been posited to be the bridge between iron accumulation and autophagy impairment in PD. In addition, iron directly interacts with α-synuclein in Lewy bodies, which are primarily digested through the autophagy–lysosome pathway. These findings indicate that some link exists between iron deposition and autophagy impairment in PD. In this review, the basic mechanisms of the autophagy–lysosome pathway and iron trafficking are introduced, and then their interaction under physiological conditions is explained. Finally, we finish by discussing the dysfunction of iron deposition and autophagy in PD, as well as their potential relationship, which will provide some insight for further study.