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  4. Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury

Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury

Int. J. Mol. Sci., 2023 · DOI: 10.3390/ijms24032791 · Published: February 1, 2023

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

Traumatic spinal cord injury (SCI) leads to neuron death and loss of function. This study investigates whether increasing the levels of a protein called X-linked inhibitor of apoptosis protein (XIAP) in neurons can protect them and improve recovery after SCI. The researchers used transgenic mice that overexpress XIAP in their neurons and a human cell line modified to overexpress XIAP. They found that increasing XIAP levels led to better neuron survival, tissue preservation, and motor recovery after SCI in mice. In the cell line, overexpression of XIAP reduced caspase activity (enzymes that promote cell death) and apoptotic cell death after exposure to harmful stimuli, suggesting that XIAP's protective effects are related to its ability to inhibit programmed cell death.

Study Duration
21-28 days post-operation
Participants
CB57BL/6 mice (WT and transgenic) and human SH-SY5Y cells
Evidence Level
Level 2: Experimental study (animal model and cell line)

Key Findings

  • 1
    Overexpression of hXIAP in neurons of transgenic mice (CB57hXIAP+) led to a significant increase in the number of surviving neurons after SCI, particularly in the penumbra regions around the injury epicenter.
  • 2
    CB57hXIAP+ mice exhibited greater white matter preservation, especially in the caudal sections close to the injury site, indicating reduced tissue damage due to hXIAP overexpression.
  • 3
    CB57hXIAP+ mice showed improved locomotor recovery compared to wild-type mice, with higher BMS scores and a greater capacity for coordinated walking, suggesting that hXIAP overexpression reduces motor skill deficits.

Research Summary

This study confirms that increasing XIAP protein expression in neurons effectively reduces caspase activity and apoptotic death in neural cells exposed to deleterious stimuli. Overexpression of XIAP protects spinal neurons from secondary damage in a mouse model of contusive SCI, contributing to tissue sparing and motor function recovery. The findings identify XIAP as an important therapeutic target for alleviating the deleterious effects of SCI by fostering neuronal survival and improving SCI outcome.

Practical Implications

Therapeutic Target Identification

XIAP is identified as a potential therapeutic target for SCI.

Neuroprotective Strategies

Increasing XIAP expression in neurons is a promising strategy to ameliorate SCI deficits.

Combination Therapies

XIAP-targeted therapies could be combined with other drugs for enhanced neuroprotection.

Study Limitations

  • 1
    The study relies on a transgenic mouse model, which may not fully replicate the complexities of human SCI.
  • 2
    The specific survival/cell death pathways regulated by XIAP overexpression in spinal cord neuronal populations require further investigation.
  • 3
    The study does not fully elucidate the mechanisms underlying XIAP cleavage after SCI and its functional consequences.

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