Journal Article

Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease

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

2022

Overview

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 xc−/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.

• Publisher: MDPI AG,MDPI
• Subject: Apoptosis / Autophagy / Blood-brain barrier / Brain / Brain - metabolism / Brain injury / Cell death / Chelating agents / Clinical trials / Coenzyme Q10 / Development and progression / Dopamine receptors / Ferroptosis / glutathione / Glutathione - metabolism / Glutathione peroxidase / Health aspects / Homeostasis / Humans / Iron / Iron - metabolism / Iron in the body / Lipid peroxidation / Mitochondria / Molecular modelling / Morphology / Movement disorders / Neurodegenerative Diseases / Oxidative stress / Parkinson disease / Parkinson Disease - drug therapy / Parkinson's disease / Pathogenesis / Phospholipid Hydroperoxide Glutathione Peroxidase - metabolism / Phospholipids / Physiology / Proteins / Review / system xc