Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease.

Kai-Jung Lin, Shang-Der Chen, Kai-Lieh Lin, Chia-Wei Liou, Min-Yu Lan, Yao-Chung Chuang, Pei-Wen Wang, Jong-Jer Lee, Feng-Sheng Wang, Hung-Yu Lin, Tsu-Kung Lin

Journal: Cells 2022;11(23):3829

PMID: 36497089

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Abstract

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system x/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood-brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.

Address: Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Family Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan.; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Center of Parkinson's Disease, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Center of Parkinson's Disease, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Neurology, Pao Chien Hospital, Pingtung 90064, Taiwan.; Department of Biological Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Metabolism, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan.

DOI: 10.3390/cells11233829

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/parkinsonsdisease.html

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-S100A4-1

MeSH Terms: Humans, Phospholipid Hydroperoxide Glutathione Peroxidase, Iron, Parkinson Disease, Neurodegenerative Diseases, Glutathione, Brain