Cyclic helix B peptide alleviates proinflammatory cell death and improves functional recovery after traumatic spinal cord injury

Redox Biology, 2023 · DOI: https://doi.org/10.1016/j.redox.2023.102767 · Published: May 30, 2023

Simple Explanation

Spinal cord injury (SCI) is a devastating condition that leads to various complications, including inflammation and cell death. This study investigates the potential of cyclic helix B peptide (CHBP) to mitigate these detrimental effects. CHBP is designed to maintain erythropoietin (EPO) activity. The research explores whether CHBP can protect nerve cells by regulating necroptosis and pyroptosis, two types of proinflammatory programmed cell death. The study employs a mouse model of SCI, using various methods like histological analysis, behavioral tests, and molecular assays to determine how CHBP impacts functional recovery, autophagy, pyroptosis, necroptosis, and related signaling pathways.

Study Duration

Not specified

Participants

436 female C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
CHBP significantly improves functional restoration after SCI.
2
CHBP elevates autophagy and suppresses pyroptosis and necroptosis following SCI.
3
CHBP-triggered elevation of autophagy is mediated by the dephosphorylation and nuclear translocation of TFEB via stimulation of the AMPK-FOXO3a-SPK2-CARM1 and AMPK-mTOR signalling pathways.

Research Summary

This study investigates the neuroprotective effects of cyclic helix B peptide (CHBP) on spinal cord injury (SCI) in mice. The results indicate that CHBP improves functional recovery by alleviating proinflammatory cell death, specifically pyroptosis and necroptosis. CHBP enhances autophagy, a cellular process that removes damaged components, and this enhancement is crucial for its protective effects. The study demonstrates that inhibiting autophagy attenuates the benefits of CHBP. The mechanism behind CHBP's action involves the activation of TFEB, a key regulator of autophagy, through the AMPK-mTOR and AMPK-FOXO3a-SPK2-CARM1 signaling pathways. This activation leads to the suppression of pyroptosis and necroptosis.

Practical Implications

Therapeutic Potential

CHBP could be a prospective therapeutic agent for clinical application in SCI patients, given its ability to alleviate proinflammatory cell death and promote functional recovery.

Targeted Autophagy

The study highlights the importance of autophagy in SCI treatment, suggesting that therapies targeting autophagy modulation could be beneficial.

Signaling Pathways

Understanding the AMPK-mTOR and AMPK-FOXO3a-SPK2-CARM1 signaling pathways in SCI can pave the way for developing more targeted and effective treatments.

Study Limitations

1
Stability of CHBP and clinical potential require additional research.
2
Intraperitoneal injection has poor translation potential in humans.
3
Lack of investigation into other cell death types following SCI, such as parthanatos and ferroptosis.

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