Johnson G V, Cox T M, Lockhart J P, Zinnerman M D, Miller M L, Powers R E
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 35294-0017, USA.
Brain Res. 1997 Mar 21;751(2):323-9. doi: 10.1016/s0006-8993(96)01431-x.
Transglutaminase is a calcium-activated enzyme that crosslinks substrate proteins into insoluble, often filamentous aggregates resistant to proteases. Because the neurofibrillary tangles in Alzheimer's disease have similar characteristics, and because tau protein, the major component of these tangles is an excellent substrate of transglutaminase in vitro, transglutaminase activity and levels were measured in control and Alzheimer's disease brain. Frozen prefrontal cortex and cerebellum samples from Alzheimer's disease and control cases matched for age and postmortem interval were used in the analyses. Total transglutaminase activity was significantly higher in the Alzheimer's disease prefrontal cortex compared to control. In addition the levels of tissue transglutaminase, as determined by quantitative immunoblotting, were elevated approximately 3-fold in Alzheimer's disease prefrontal cortex compared to control. To our knowledge, this is the first demonstration that transglutaminase is increased in Alzheimer's disease brain. There were no significant differences in transglutaminase activity or levels in the cerebellum between control and Alzheimer's disease cases. Because the elevation of transglutaminase in the Alzheimer's disease samples occurred in the prefrontal cortex, where neurofibrillary pathology is usually abundant, and not in the cerebellum, which is usually spared in Alzheimer's disease, it can be suggested that transglutaminase could be a contributing factor in neurofibrillary tangle formation.
转谷氨酰胺酶是一种钙激活酶，它能将底物蛋白交联成不溶性的、通常为丝状的聚集体，这些聚集体对蛋白酶具有抗性。由于阿尔茨海默病中的神经原纤维缠结具有相似的特征，并且由于这些缠结的主要成分tau蛋白在体外是转谷氨酰胺酶的优良底物，因此在对照和阿尔茨海默病大脑中测量了转谷氨酰胺酶的活性和水平。分析中使用了来自阿尔茨海默病和对照病例的冷冻前额叶皮质和小脑样本，这些样本在年龄和死后间隔方面相匹配。与对照相比，阿尔茨海默病前额叶皮质中的总转谷氨酰胺酶活性显著更高。此外，通过定量免疫印迹法测定，与对照相比，阿尔茨海默病前额叶皮质中的组织转谷氨酰胺酶水平升高了约3倍。据我们所知，这是首次证明阿尔茨海默病大脑中转谷氨酰胺酶增加。对照和阿尔茨海默病病例的小脑中转谷氨酰胺酶活性或水平没有显著差异。由于阿尔茨海默病样本中转谷氨酰胺酶的升高发生在前额叶皮质，那里神经原纤维病理通常很丰富，而不在小脑中，小脑在阿尔茨海默病中通常不受影响，因此可以认为转谷氨酰胺酶可能是神经原纤维缠结形成的一个促成因素。
