Paclitaxel alleviates spinal cord injury via activation of the Wnt/β-catenin signaling pathway

TL;DR

Paclitaxel helps recover from spinal cord injury by activating a key signaling pathway, suggesting a new treatment approach.

Contribution

The study reveals that paclitaxel's neuroprotective effects in spinal cord injury are mediated through the Wnt/β-catenin signaling pathway.

Findings

Paclitaxel improved lower limb function and reduced neuronal damage after spinal cord injury.

Activation of the Wnt/β-catenin pathway was crucial for paclitaxel's therapeutic effects.

Blocking the Wnt/β-catenin pathway negated the benefits of paclitaxel in injured mice.

Abstract

Spinal cord injury (SCI) is a disability that causes severe traumatic damage to the central nervous system, with increasing prevalence worldwide. Paclitaxel (PTX) is a naturally occurring plant metabolite that has been shown to exhibit various neuroprotective effects in the central nervous system, however, the specific mechanisms underlying its protective effects in SCI remain unclear. In this study, we aimed to explore the therapeutic effects of PTX in SCI, as well as elucidate the underlying molecular mechanisms associated with its neuroprotective potential.

Murine models of spinal cord compression were performed followed by intrathecal administration of corresponding agents for 21 days. Mice were randomly divided into the following four groups: Sham, SCI + Saline, SCI + PTX, and SCI + PTX + XAV939. Recovery of lower limb function and strength, as well as muscular atrophy were examined via multiple scored tests. Degree of neuronal and axonal damage, as well as fibrosis were examined via immunohistochemical staining.

PTX administration significantly improved the recovery of lower limb function and strength, prevented muscular atrophy, as well as decreased the extent of neuronal and axonal death following SCI surgery. PTX also robustly activated the Wnt/β-catenin protein signaling pathway that played a key role in its therapeutic effects. Co-administration with a Wnt/β-catenin pathway inhibitor - XAV939, significantly abolished the beneficial effects of PTX after SCI.

This study provides important new mechanistic insight on the beneficial effects of PTX in protecting against spinal cord injury, as well as the experimental basis for its potential therapeutic use.

The online version contains supplementary material available at 10.1186/s10020-025-01240-3.

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