Melli Giorgia, Jack Christelene, Lambrinos George L, Ringkamp Mathias, Höke Ahmet
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Neurobiol Dis. 2006 Dec;24(3):525-30. doi: 10.1016/j.nbd.2006.08.014. Epub 2006 Sep 28.
Paclitaxel causes a sensory polyneuropathy with characteristic features of distal axonal degeneration. Although the exact mechanisms underlying distal axonal degeneration are unknown, paclitaxel-induced axonal degeneration has been shown to be associated with an increase in detyrosinated tubulin. Here we show that recombinant human erythropoietin prevents axonal degeneration in sensory neurons in vitro and this effect is associated with downregulation of detyrosinated tubulin. Furthermore, in an animal model of paclitaxel-induced distal sensory polyneuropathy, recombinant human erythropoietin protects against distal axonal degeneration. These findings suggest that recombinant human erythropoietin may be useful as a therapy to prevent paclitaxel-induced sensory polyneuropathy in patients undergoing chemotherapy.
紫杉醇会引发一种具有远端轴突退化特征的感觉性多发性神经病变。尽管远端轴突退化的确切机制尚不清楚,但已表明紫杉醇诱导的轴突退化与去酪氨酸化微管蛋白的增加有关。在此我们表明,重组人促红细胞生成素在体外可预防感觉神经元中的轴突退化,且这种作用与去酪氨酸化微管蛋白的下调有关。此外,在紫杉醇诱导的远端感觉性多发性神经病变动物模型中,重组人促红细胞生成素可预防远端轴突退化。这些发现表明,重组人促红细胞生成素可能作为一种疗法,用于预防接受化疗患者的紫杉醇诱导的感觉性多发性神经病变。