Matsumoto A, Enomoto T, Fujiwara Y, Baba H, Matsumoto R
Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
Neurosci Lett. 1996 Dec 20;220(3):159-62. doi: 10.1016/s0304-3940(96)13235-3.
To explore whether extracellular matrix components in human brain affect the deposition and aggregation of beta-amyloid containing peptides, human brain samples from patients with sporadic Alzheimer's disease and normal aged were analyzed by Western blot analysis. All major beta-amyloid-containing peptides contained epitope(s) which is recognized by anti heparan sulfate antibody. Incubation of brain beta-amyloid-containing peptides with human collagen type IV in neutral pH efficiently generated a high molecular weight aggregated band, approximately 5-fold that of the control sample. We have previously found a serine protease which is capable of cleaving an oligopeptide at the N-terminus of beta-amyloid. In this study, the protease, which also contains heparan sulfate glycoconjugates, degraded the above brain peptides as natural substrates, although with different efficiency. These findings suggest that extra-cellular matrix components affect the processing and aggregation of beta-amyloid-containing peptides in human brain.
为探究人脑中的细胞外基质成分是否会影响含β-淀粉样肽的沉积和聚集，我们通过蛋白质免疫印迹分析对散发性阿尔茨海默病患者和正常老年人的人脑样本进行了分析。所有主要的含β-淀粉样肽都含有可被抗硫酸乙酰肝素抗体识别的表位。在中性pH条件下，将脑内含β-淀粉样肽与人IV型胶原一起孵育，能有效产生一条高分子量聚集带，其大小约为对照样本的5倍。我们之前发现了一种丝氨酸蛋白酶，它能够在β-淀粉样肽的N端切割一个寡肽。在本研究中，这种同样含有硫酸乙酰肝素糖缀合物的蛋白酶，将上述脑肽作为天然底物进行降解，不过降解效率有所不同。这些发现表明，细胞外基质成分会影响人脑中含β-淀粉样肽的加工和聚集。
