Ferroptosis is a new therapeutic target for spinal cord injury

Frontiers in Neuroscience, 2023 · DOI: 10.3389/fnins.2023.1136143 · Published: March 14, 2023

Simple Explanation

Spinal cord injury (SCI) is a serious traumatic disease, often resulting from car accidents and falls, leading to disability and psychological disorders. Current treatments are not satisfactory, highlighting the need for new methods. Ferroptosis, a programmed cell death, involves iron overload, ROS accumulation, lipid peroxidation, and glutamate accumulation. These factors are also present in SCI, suggesting Ferroptosis's role in secondary injury. This review explores the relationship between Ferroptosis and SCI, listing substances that improve SCI by inhibiting Ferroptosis. It also discusses challenges in clinically translating Ferroptosis inhibitors, aiming to accelerate their use in SCI treatment.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Iron overload in the motor cortex induces neuronal Ferroptosis following spinal cord injury. Iron deposition in the motor cortex was significantly increased in SCI patients compared to healthy controls.
2
GPX4 knockout-induced degeneration of spinal motor neurons exhibits Ferroptosis. Supplementing with vitamin E, a Ferroptosis inhibitor, delayed paralysis and death in GPX4 knockout-induced mice.
3
Substances like proanthocyanidins, epigallocatechin gallate, and zinc can improve motor recovery after SCI by inhibiting Ferroptosis, providing further evidence for their clinical application.

Research Summary

This review explores the connection between Ferroptosis and spinal cord injury (SCI), highlighting that iron overload, ROS accumulation, lipid peroxidation, and glutamate accumulation—all associated with Ferroptosis—are present in SCI. Several substances, including proanthocyanidins and epigallocatechin gallate, are listed as potential treatments for SCI by inhibiting Ferroptosis. These substances often upregulate the expression of GSH, GPX4, and Nrf2 while downregulating ACSL4 and iron. The review discusses potential problems in the clinical translation of Ferroptosis inhibitors, such as the mode of administration, dosing, and timing. It also suggests focusing future research on non-coding RNAs and the exploration of novel drugs.

Practical Implications

Therapeutic Target

Ferroptosis inhibition presents a promising therapeutic target for spinal cord injury.

Drug Development

Focus on developing drugs that modulate key Ferroptosis regulators like GPX4, FSP1, and Nrf2.

Clinical Translation

Address challenges in drug delivery across the blood-brain barrier and optimize dosing regimens for clinical use.

Study Limitations

1
Most studies are at the animal stage, limiting direct translation to humans.
2
The exact downstream target proteins and enzymes affected by substances through the Nrf2 pathway to inhibit Ferroptosis and treat SCI have not been clearly investigated.
3
Clinical translation of Ferroptosis inhibitors faces challenges such as poor in vivo solubility and short half-life.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury