Document Type
Article
Publication Date
2022
Keywords
α-synuclein, Ferritin, Iron, Autophagy, Ferritinophagy, Vesicular Trafficking, Parkinson’s Disease, Neurodegeneration
Digital Object Identifier (DOI)
https://doi.org/10.3390/ijms23042378
Abstract
A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.
Rights Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
International Journal of Molecular Sciences, v. 23, issue 4, art. 2378
Scholar Commons Citation
Boag, Matthew K.; Roberts, Angus; Uversky, Vladimir N.; Ma, Linlin; Richardson, Des R.; and Pountney, Dean L., "Ferritinophagy and α-synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson’s Disease" (2022). Molecular Medicine Faculty Publications. 945.
https://digitalcommons.usf.edu/mme_facpub/945
