DeWitt D A, Silver J, Canning D R, Perry G
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106-4901.
Exp Neurol. 1993 Jun;121(2):149-52. doi: 10.1006/exnr.1993.1081.
Chondroitin sulfate proteoglycans (CSPG) are extracellular matrix proteins inhibitory to neurite outgrowth in vitro and correlated with decreased neurite outgrowth after CNS injury. Previously, heparan sulfate proteoglycan and dermatan sulfate proteoglycan have been shown to be associated with senile plaques (SPs) and neurofibrillary tangles (NFTs) but CSPG was not. In an immunocytochemical study, three monoclonal antibodies to different sulfation states of the chondroitin glycosaminoglycan were used to localize CSPG in cases of Alzheimer's disease. Chondroitin 4-sulfate was found in both SPs and NFTs. An antibody to unsulfated chondroitin strongly immunostained intracellular NFTs and the dystrophic neurites of SPs. Chondroitin 6-sulfate was found in NFTs and the area around SPs. These results suggest that CSPG, in addition or as an alternative to beta-amyloid protein, could be responsible for the regression of neurites around senile plaques in Alzheimer's disease.
硫酸软骨素蛋白聚糖(CSPG)是细胞外基质蛋白,在体外对神经突生长具有抑制作用,且与中枢神经系统损伤后神经突生长减少相关。此前,已证明硫酸乙酰肝素蛋白聚糖和硫酸皮肤素蛋白聚糖与老年斑(SPs)和神经原纤维缠结(NFTs)有关,但CSPG并非如此。在一项免疫细胞化学研究中,使用了三种针对硫酸软骨素糖胺聚糖不同硫酸化状态的单克隆抗体,以在阿尔茨海默病病例中定位CSPG。在SPs和NFTs中均发现了硫酸软骨素4-硫酸酯。一种针对未硫酸化硫酸软骨素的抗体对细胞内NFTs和SPs的营养不良性神经突进行了强烈免疫染色。在NFTs和SPs周围区域发现了硫酸软骨素6-硫酸酯。这些结果表明,CSPG除了或作为β-淀粉样蛋白的替代物,可能是阿尔茨海默病中围绕老年斑的神经突退化的原因。