The Latest View on the Mechanism of Ferroptosis and Its Research Progress in Spinal Cord Injury

Oxidative Medicine and Cellular Longevity, 2020 · DOI: https://doi.org/10.1155/2020/6375938 · Published: August 28, 2020

Spinal Cord Injury Neurology Genetics

Simple Explanation

Ferroptosis is a recently discovered type of cell death distinct from apoptosis, characterized by iron dependence and accumulation of lipid reactive oxygen species (ROS). This process involves specific morphological changes like shrunken mitochondria. The mechanism of ferroptosis involves iron overloading, lipid peroxidation, and downstream execution. Regulation of ferroptosis involves pathways like glutathione/glutathione peroxidase 4, the mevalonate pathway, and the transsulfuration pathway. Recent research highlights the crucial role of selenium in glutathione peroxidase 4 (GPX4) and its ability to suppress ferroptosis. Also, the discovery of ferroptosis suppressor protein 1 (FSP1) has expanded our understanding of ferroptosis mechanisms.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Ferroptosis is linked to spinal cord injury (SCI) in animal models. Inhibiting ferroptosis shows promise in promoting neurological function recovery after SCI.
2
The review focuses on the execution mechanisms of ferroptosis, particularly concerning selenium and ferroptosis suppressor protein 1 (FSP1), and summarizes current research on ferroptosis in spinal cord injury.
3
After SCI, local iron overload and increased ROS contribute to ferroptosis. Inhibiting ferroptosis can promote motor function recovery by reducing redox damage and inflammation.

Research Summary

Ferroptosis is a nonapoptotic cell death mechanism marked by iron dependence and lipid peroxidation, contributing to various diseases, including nervous system disorders and spinal cord injury. The mechanisms of ferroptosis involve iron metabolism, lipid peroxidation, and ROS accumulation, regulated by pathways like GPX4, the mevalonate pathway, and FSP1-mediated pathways. In spinal cord injury, ferroptosis contributes to secondary injury. Targeting ferroptosis through inhibitors like DFO and SRS16-86 shows promise in promoting functional recovery.

Practical Implications

Therapeutic Potential in SCI

Inhibiting ferroptosis may offer a new therapeutic strategy for promoting neurological recovery and reducing secondary damage in spinal cord injury patients.

Targeted Drug Development

Understanding the specific mechanisms of ferroptosis, especially related to selenium and FSP1, can facilitate the development of targeted drugs to combat SCI.

Clinical Application of Selenium

Further research into selenium's role in preventing ferroptosis may pave the way for its clinical application in SCI treatment.

Study Limitations

1
Detailed mechanisms of iron metabolism and subsequent oxidation reactions in ferroptosis are not fully understood.
2
The precise mechanism of the FSP1/CoQ10/DADH pathway, including how FSP1 enters the cell membrane and reduces CoQ10, remains unclear.
3
The relationship and interactions between ferroptosis, apoptosis, and autophagy in SCI require further exploration.

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