TROY and LINGO-1 expression in astrocytes and macrophages/microglia in multiple sclerosis lesions
TROY and LINGO-1 expression in astrocytes and macrophages/microglia in multiple sclerosis lesions
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DOI：
10.1111/j.1365-2990.2006.00787.x
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发表时间：
2007-02-01
影响因子：
5
通讯作者：
Konno, H.
中科院分区：
文献类型：
--
作者：
Satoh, J.;Tabunoki, H.;Konno, H.
Nogo是一个神经突起生长抑制剂家族，它导致成年中枢神经系统（CNS）轴突再生的失败。Nogo-A仅在少突胶质细胞上表达，其中Nogo-66片段与神经元轴突上表达的Nogo受体（NgR）结合。NgR信号传导需要辅助受体p75（NTR）或TROY与衔接子LINGO-1的组合。为了表征在人类中枢神经系统中表达NgR复合物的细胞类型，我们通过免疫组织化学研究了多发性硬化（MS）脑的脱髓鞘病变。TROY和LINGO-1在反应性星形胶质细胞、巨噬细胞/小胶质细胞和神经元的亚群中被鉴定，但在少突胶质细胞中未被鉴定。TROY上调，而LINGO-1在MS脑中通过Western印迹降低。这些结果表明，NgR/TROY/LINGO-1的三元复合物表达在星形胶质细胞，巨噬细胞/小胶质细胞和神经元上，通过与少突胶质细胞上的Nogo-A相互作用，可能调节MS脱髓鞘病变中的胶质-神经元相互作用。
Nogo constitutes a family of neurite outgrowth inhibitors contributing to a failure of axonal regeneration in the adult central nervous system (CNS). Nogo-A is expressed exclusively on oligodendrocytes where Nogo-66 segment binds to Nogo receptor (NgR) expressed on neuronal axons. NgR signalling requires a coreceptor p75(NTR) or TROY in combination with an adaptor LINGO-1. To characterize the cell types expressing the NgR complex in the human CNS, we studied demyelinating lesions of multiple sclerosis (MS) brains by immunohistochemistry. TROY and LINGO-1 were identified in subpopulations of reactive astrocytes, macrophages/microglia and neurones but not in oligodendrocytes. TROY was up-regulated, whereas LINGO-1 was reduced in MS brains by Western blot. These results suggest that the ternary complex of NgR/TROY/LINGO-1 expressed on astrocytes, macrophages/microglia and neurones, by interacting with Nogo-A on oligodendrocytes, might modulate glial-neuronal interactions in demyelinating lesions of MS.