The role of mTOR signaling pathway in spinal cord injury

Cell Cycle, 2012 · DOI: 10.4161/cc.21262 · Published: September 1, 2012

Simple Explanation

The mTOR signaling pathway is important for cell functions like metabolism, growth, and survival. Studies suggest it has both protective and regenerative roles in the central nervous system after trauma or disease. Researchers found that blocking mTOR with rapamycin reduced damage and improved movement after spinal cord injury in mice. This suggests mTOR inhibition could protect nerve tissue and reduce secondary damage after such injuries. Following a spinal cord injury (SCI), the body undergoes several phases of damage and repair. Initially, the spinal cord suffers direct damage. Subsequently, secondary injury processes are activated, leading to further tissue damage. Later, regenerative processes begin, including axonal regeneration and remyelination. The role of mTOR signaling varies across these phases, affecting cell death, inflammation, and tissue regeneration differently. Inhibiting mTOR might slow down cellular aging in the nervous system, potentially preserving the ability to regenerate after a spinal cord injury. This could be especially beneficial for older patients, as the natural ability to recover from such injuries tends to decline with age. Therefore, treatments involving rapamycin may help improve regenerative capacity in older individuals with spinal cord injuries.

Study Duration

Not specified

Participants

Mice

Evidence Level

Review article

Key Findings

1
Inhibition of mTOR reduces cell death in damaged neural tissue following SCI.
2
Inhibition of mTOR reduces the levels of pro-inflammatory markers and NO synthase activity that are induced by cytokines in microglia.
3
The role of mTOR in injured spinal cords may differ depending on the time phase following SCI.

Research Summary

The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. SCI involves multiple pathophysiological and regenerative processes. These processes vary depending on the time phase after the initial onset of injury. Many previous experimental studies using CNS injury models have demonstrated promising effects of mTOR inhibition to reduce neural tissue damage.

Practical Implications

Therapeutic Target for SCI

mTOR inhibition may be a viable therapeutic target for reducing secondary damage in patients with SCI.

Clinical Applications

Further research is needed to clarify the mechanisms regulated by mTOR signaling in order to approve clinical use of mTOR inhibitors in patients with acute SCI.

Angiogenesis Stimulation

Modulating the mTOR signaling pathway to stimulate angiogenesis may be a promising approach to promote neuroregeneration after SCI.

Study Limitations

1
The actual molecular mechanisms underlying the neuroprotective effects regulated by the mTOR signaling pathway remain to be elucidated.
2
The distinct mechanisms of interaction between the activation of autophagy and cell death are also unknown.
3
The clinical applications of mTOR inhibitors for CNS injury have not yet been established.

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