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  4. Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury

Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury

Nature, 2015 · DOI: 10.1038/nature13974 · Published: February 19, 2015

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Spinal cord injury (SCI) often results in disabilities due to limited nerve regeneration. The body creates barriers, specifically glial scars, that prevent nerve regrowth. The study found that Protein Tyrosine Phosphatase σ (PTPσ) plays a critical role in preventing nerve growth by stabilizing growth cones within these inhibitory substrates. A peptide was created to bind to PTPσ and reduce its inhibitory effects. Administering this peptide led to the restoration of nerve connections and improved the recovery of locomotor and urinary functions after spinal cord injury.

Study Duration
7 weeks
Participants
Adult female Sprague-Dawley rats (225–250g)
Evidence Level
Not specified

Key Findings

  • 1
    PTPσ stabilizes growth cones within CSPG-rich substrates, contributing to axonal dystrophy.
  • 2
    A novel peptide mimetic (ISP) of the PTPσ wedge domain binds to PTPσ and relieves CSPG-mediated inhibition in vitro.
  • 3
    Systemic delivery of ISP after SCI restores serotonergic innervation and facilitates functional recovery of locomotor and urinary systems.

Research Summary

This study investigates the role of PTPσ in inhibiting nerve regeneration after spinal cord injury (SCI). A peptide mimetic (ISP) targeting PTPσ was developed and tested for its ability to promote recovery after SCI. The results demonstrate that ISP treatment can restore nerve connections and improve functional outcomes in rats with SCI.

Practical Implications

Therapeutic Potential

Systemic modulation of PTPσ offers a new avenue for non-invasive treatments to enhance functional recovery following injuries where proteoglycans inhibit axon regeneration.

Drug Development

The Intracellular Sigma Peptide (ISP) can be further optimized to improve its efficacy in treating spinal cord injuries and other conditions involving CSPG-mediated inhibition.

Understanding Axonal Dystrophy

The research highlights a key cellular mechanism regulated by PTPσ that leads to axonal dystrophy, providing insights for preventing chronic regeneration failure.

Study Limitations

  • 1
    The study was conducted on rats, and further research is needed to determine the efficacy and safety of ISP in humans.
  • 2
    The study did not observe lengthy regenerating BDA labeled cortico-spinal tract fibers.
  • 3
    Variability in spared tissue correlated with functional recovery in vehicle, but not ISP treated animals

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