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Published on: May 4, 2020
Ferroptosis at the crossroads of manganese-induced neurotoxicity: A retrospective study
Yaoyang Liu1, Shanyu Lv1, Guoguo He1
1Department of Toxicology, College of Public Health, Guilin Medical University, Guilin, China.
Abstract:
Manganese is an essential trace element, but overexposure can cause neurotoxicity and subsequent neurodegenerative diseases. Ferroptosis is a form of cell death characterized by lipid peroxidation and iron overload inside cells, which is closely related to manganese neurotoxicity. Manganese can induce ferroptosis through multiple pathways: causing oxidative stress and increased cellular reactive oxygen species (ROS), resulting in lipid peroxidation; depleting glutathione (GSH) and weakening the antioxidant capacity of cells; disrupting iron metabolism and increasing iron-dependent lipid peroxidation; damaging mitochondrial function and disrupting the electron transport chain, leading to increased ROS production. Oxidative stress, iron metabolism disorders, lipid peroxidation, GSH depletion, and mitochondrial dysfunction, typical features of ferroptosis, have been observed in animal and cell models after manganese exposure. In summary, manganese can participate in the pathogenesis of neurodegenerative diseases by inducing events related to ferroptosis. This provides new insights into studying the mechanism of manganese neurotoxicity and developing therapeutic drugs.
Insights
Manganese overexposure triggers ferroptosis, a cell death pathway involving lipid peroxidation and iron overload. This finding offers new insights into manganese neurotoxicity and potential therapeutic strategies for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Manganese is essential but toxic at high levels, linked to neurodegeneration.
- Ferroptosis, a cell death type, involves lipid peroxidation and iron accumulation.
- Ferroptosis is implicated in manganese-induced neurotoxicity.
Purpose of the Study:
- To elucidate the role of ferroptosis in manganese neurotoxicity.
- To explore the molecular mechanisms linking manganese exposure to ferroptosis.
- To identify potential therapeutic targets for manganese neurotoxicity.
Main Methods:
- Review of existing literature on manganese toxicity and ferroptosis.
- Analysis of pathways involved in manganese-induced oxidative stress and iron dysregulation.
- Examination of cellular and animal models of manganese exposure.
Main Results:
- Manganese exposure induces oxidative stress, depletes glutathione (GSH), and disrupts iron metabolism.
- These disruptions lead to lipid peroxidation and mitochondrial dysfunction, hallmarks of ferroptosis.
- Ferroptotic events are observed in models following manganese exposure.
Conclusions:
- Manganese exposure can induce ferroptosis through multiple interconnected pathways.
- Ferroptosis is a key mechanism in manganese neurotoxicity and associated neurodegenerative diseases.
- Understanding this link may lead to novel therapeutic interventions.
