Berger Philipp, Sirkowski Erich E, Scherer Steven S, Suter Ueli
Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
Neurobiol Dis. 2004 Nov;17(2):290-9. doi: 10.1016/j.nbd.2004.07.014.
Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1) lead to truncations of the encoded protein and are associated with an autosomal recessive demyelinating neuropathy--hereditary motor and sensory neuropathy-Lom. NDRG1 protein is highly expressed in peripheral nerve and is localized in the cytoplasm of myelinating Schwann cells, including the paranodes and Schmidt-Lanterman incisures. In contrast, sensory and motor neurons as well as their axons lack NDRG1. NDRG1 mRNA levels in developing and injured adult sciatic nerves parallel those of myelin-related genes, indicating that the expression of NDRG1 in myelinating Schwann cells is regulated by axonal interactions. Oligodendrocytes also express NDRG1, and the subtle CNS deficits of affected patients may result from a lack of NDRG1 in these cells. Our data predict that the loss of NDRG1 leads to a Schwann cell autonomous phenotype resulting in demyelination, with secondary axonal loss.
编码N - myc下游调节基因-1（NDRG1）的基因突变会导致编码蛋白的截短，并与常染色体隐性脱髓鞘性神经病——遗传性运动和感觉神经病-Lom相关。NDRG1蛋白在外周神经中高度表达，定位于髓鞘形成雪旺细胞的细胞质中，包括结旁区和施密特-兰尔特曼切迹。相比之下，感觉神经元、运动神经元及其轴突缺乏NDRG1。发育中和损伤后的成年坐骨神经中NDRG1 mRNA水平与髓鞘相关基因的水平平行，表明髓鞘形成雪旺细胞中NDRG1的表达受轴突相互作用调控。少突胶质细胞也表达NDRG1，受影响患者轻微的中枢神经系统缺陷可能是由于这些细胞中缺乏NDRG1所致。我们的数据预测，NDRG1的缺失会导致雪旺细胞自主表型，从而导致脱髓鞘，并继发轴突丧失。
