Kato S, Horiuchi S, Nakashima K, Hirano A, Shibata N, Nakano I, Saito M, Kato M, Asayama K, Ohama E
Division of Neuropathology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Acta Neuropathol. 1999 Mar;97(3):260-6. doi: 10.1007/s004010050983.
To clarify the neuropathological significance of the deposition of N(epsilon)-carboxymethyl lysine (CML), an advanced glycation endproduct, in astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis (FALS), autopsy specimens from five members of two different families who had the superoxide dismutase 1 (SOD1) gene mutations were analysed. Immunohistochemically, most of the neuronal and astrocytic hyaline inclusions were intensely stained by the antibody against CML. The distributions and intensities of the immunoreactivities for CML and SOD1 were similar in the inclusions in both cell types. Immunoelectron microscopy showed that both inclusions consisted of CML-positive granule-coated fibrils and granular materials. No significant CML or SOD1 immunoreactivity was observed in the neurons and astrocytes of the normal control subjects. Our results suggest that astrocytic hyaline inclusions contain CML and SOD1 in FALS patients with SOD1 gene mutations, and that the formation of CML-modified protein (probably CML-modified SOD1) is related to the cell degeneration.
为阐明晚期糖基化终产物N(ε)-羧甲基赖氨酸（CML）在家族性肌萎缩侧索硬化症（FALS）星形细胞透明包涵体中的沉积的神经病理学意义，对两个不同家族的五名携带超氧化物歧化酶1（SOD1）基因突变成员的尸检标本进行了分析。免疫组织化学分析显示，大多数神经元和星形细胞透明包涵体被抗CML抗体强烈染色。CML和SOD1免疫反应的分布和强度在两种细胞类型的包涵体中相似。免疫电子显微镜显示，两种包涵体均由CML阳性颗粒包被的原纤维和颗粒物质组成。在正常对照受试者的神经元和星形细胞中未观察到明显的CML或SOD1免疫反应。我们的结果表明，在携带SOD1基因突变的FALS患者中，星形细胞透明包涵体含有CML和SOD1，并且CML修饰蛋白（可能是CML修饰的SOD1）的形成与细胞变性有关。
