Health Risk Research Section, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8606, Japan.
Neurotoxicology. 2012 Oct;33(5):1375-80. doi: 10.1016/j.neuro.2012.08.016. Epub 2012 Sep 7.
Thalidomide is increasingly used in anticancer and anti-inflammation therapies. However, it is known for its teratogenicity and ability to induce peripheral neuropathy, although the mechanisms underlying its neurological effect in humans are unclear. In this study, we investigated the effect of thalidomide on the metabolism and neuronal differentiation of human neural progenitor cells. We found that levels of tyrosine, phenylalanine, methionine and glutathione, which are involved in dopamine and methionine metabolism, were decreased following thalidomide treatment. Morphological analysis revealed that treatment with 100 nM thalidomide, which is much lower than clinical doses, significantly decreased the number of dopaminergic (tyrosine hydroxylase-positive) neurons, compared with control cells. Our results suggest that these adverse neurological effects of thalidomide should be taken into consideration prior to its use for the treatment of neurodegenerative and other diseases.
沙利度胺越来越多地用于癌症治疗和抗炎治疗。然而，它具有致畸性和诱导周围神经病的能力，尽管其在人类中的神经作用机制尚不清楚。在这项研究中，我们研究了沙利度胺对人神经祖细胞代谢和神经元分化的影响。我们发现，参与多巴胺和蛋氨酸代谢的酪氨酸、苯丙氨酸、蛋氨酸和谷胱甘肽的水平在沙利度胺处理后降低。形态分析表明，与对照细胞相比，100 nM 沙利度胺（远低于临床剂量）的处理显著减少了多巴胺能（酪氨酸羟化酶阳性）神经元的数量。我们的结果表明，在将沙利度胺用于治疗神经退行性疾病和其他疾病之前，应考虑其这些不良的神经作用。
