Ichai C, Chevallier N, Delaere P, Dournaud P, Epelbaum J, Hauw J J, Vincent J P, Checler F
Institut de Pharmacologie Moléculaire et Cellulaire, UPR 411 CNRS, Valbonne, France.
J Neurochem. 1994 Feb;62(2):645-55. doi: 10.1046/j.1471-4159.1994.62020645.x.
We established the cartography of 11 exo- and endopeptidases in the frontal and parietal cortices and in the cerebellum of brains of patients diagnosed with a senile dementia of the Alzheimer's type (SDAT). Comparison with those of four subjects who had died without known neurologic or psychiatric illness indicated that there existed a region-specific alteration of the peptidase contents in the disease. In the frontal area of SDAT brains, postproline dipeptidyl aminopeptidase and aminopeptidase M activities were significantly reduced. In the parietal cortex of SDAT brain, activities of three additional endopeptidases--angiotensin-converting enzyme, proline endopeptidase, and endopeptidase 24.15--were also drastically reduced. In contrast, the cerebellum displayed a set of proteolytic activities that remained unaffected in SDAT brain. The putative influence of the disease on the catabolic fates of neurotensin, neuropeptide Y, and somatostatin(1-14) was investigated. Neurotensin was catabolized at identical rates in the frontal and parietal cortices in nondemented and SDAT brains. In contrast, neuropeptide Y metabolism was slowed down in SDAT brains in the frontal but not in the parietal cortex. Finally, the degradation velocities of somatostatin(1-14) were lowered in both cortical areas of SDAT brains. It is interesting that, by means of specific peptidase inhibitors, we demonstrated that endopeptidase 24.15 participated in somatostatin(1-14) inactivation in the parietal but not in the frontal cortex. It is suggested that the lowering of the rate of somatostatin(1-14) inactivation in the parietal cortex of SDAT brains likely results from the depletion of endopeptidase 24.15 in this brain region.
我们绘制了被诊断为阿尔茨海默病型老年痴呆症（SDAT）患者大脑额叶、顶叶皮质及小脑中11种外肽酶和内肽酶的分布图。与4名无已知神经或精神疾病而死亡者的大脑进行比较表明，该疾病中肽酶含量存在区域特异性改变。在SDAT患者大脑的额叶区域，脯氨酰二肽基氨基肽酶和氨肽酶M的活性显著降低。在SDAT患者大脑的顶叶皮质中，另外三种内肽酶——血管紧张素转换酶、脯氨酸内肽酶和内肽酶24.15的活性也大幅降低。相比之下，小脑呈现出一组蛋白水解活性，在SDAT患者大脑中未受影响。研究了该疾病对神经降压素、神经肽Y和生长抑素（1 - 14）分解代谢命运的假定影响。在非痴呆和SDAT患者大脑的额叶和顶叶皮质中，神经降压素的分解代谢速率相同。相比之下，在SDAT患者大脑中，神经肽Y在额叶皮质的代谢减缓，但在顶叶皮质未减缓。最后，在SDAT患者大脑的两个皮质区域中，生长抑素（1 - 14）的降解速度均降低。有趣的是，通过特异性肽酶抑制剂，我们证明内肽酶24.15参与了顶叶皮质而非额叶皮质中生长抑素（1 - 14）的失活。提示SDAT患者大脑顶叶皮质中生长抑素（1 - 14）失活速率的降低可能是由于该脑区中内肽酶24.15的耗竭所致。
