F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA.
Neuropharmacology. 2014 Jan;76 Pt A:175-83. doi: 10.1016/j.neuropharm.2013.08.016. Epub 2013 Aug 24.
Paclitaxel is a microtubule-binding compound that is widely used as a chemotherapeutic in the treatment of common cancers, including breast and ovarian cancer. Paclitaxel binding along the length of microtubules stabilizes them and suppresses their dynamics, leading to mitotic arrest and apoptosis in dividing cells. Though they are not dividing cells, neurons are also susceptible to paclitaxel, and paclitaxel exposure results in axonal degeneration. Thus a frequent side effect of paclitaxel treatment in patients is peripheral neuropathy, which can necessitate dose reductions and have lasting symptoms. An understanding of the mechanisms underlying paclitaxel's neurotoxicity is important for development of therapeutics to prevent and alleviate the neuropathy. Here we will review approaches taken to investigate mechanisms of paclitaxel-induced neuropathy and evidence for potential mechanisms of the axonal degeneration downstream of or distinct from microtubule stabilization by paclitaxel. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.
紫杉醇是一种微管结合化合物，广泛用作治疗常见癌症（包括乳腺癌和卵巢癌）的化疗药物。紫杉醇结合在微管的长度上稳定它们并抑制它们的动力学，导致有丝分裂停滞和分裂细胞的细胞凋亡。尽管神经元不是分裂细胞，但它们也容易受到紫杉醇的影响，紫杉醇暴露导致轴突退化。因此，紫杉醇治疗患者的常见副作用是周围神经病，这可能需要减少剂量并产生持久的症状。了解紫杉醇神经毒性的机制对于开发预防和减轻神经病的治疗方法非常重要。在这里，我们将回顾研究紫杉醇诱导的神经病机制的方法，并为紫杉醇稳定微管下游或独立于微管稳定的轴突退化的潜在机制提供证据。本文是专题“神经退行性疾病的突触基础”的一部分。
