McDermott J R, Gibson A M
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK.
Neuroreport. 1996 Sep 2;7(13):2163-6. doi: 10.1097/00001756-199609020-00021.
The aim of the study was to identify and characterize human brain peptidases capable of degrading Alzheimer's beta-amyloid protein. Synthetic beta-amyloid protein (1-40) was rapidly degraded by a human brain soluble fraction, optimum activity occurring at around pH4. Pepstatin totally inhibited the activity showing that an aspartyl protease was responsible. HPLC separation and identification of the degradation products showed that the L34-M35 bond was the primary site of cleavage followed by hydrolysis of the F19-F20 and F20-A21 bonds. The major lysosomal aspartyl protease, cathepsin D, hydrolysed beta-amyloid protein with the same pH profile, inhibitor sensitivity and bond specificity as the activity present in human brain soluble fraction. We suggest that cathepsin D may play an important role in regulating brain concentrations of beta-amyloid protein (1-40).
该研究的目的是鉴定和表征能够降解阿尔茨海默病β-淀粉样蛋白的人脑肽酶。合成的β-淀粉样蛋白（1-40）被人脑可溶性组分迅速降解，最佳活性出现在pH4左右。胃蛋白酶抑制剂完全抑制了该活性，表明天冬氨酸蛋白酶是起作用的酶。通过高效液相色谱法分离和鉴定降解产物表明，L34-M35键是主要的切割位点，随后是F19-F20和F20-A21键的水解。主要的溶酶体天冬氨酸蛋白酶组织蛋白酶D，以与人脑可溶性组分中存在的活性相同的pH谱、抑制剂敏感性和键特异性水解β-淀粉样蛋白。我们认为组织蛋白酶D可能在调节脑内β-淀粉样蛋白（1-40）的浓度方面发挥重要作用。
