Shimohama S, Ninomiya H, Saitoh T, Terry R D, Fukunaga R, Taniguchi T, Fujiwara M, Kimura J, Kameyama M
Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
J Neural Transm Suppl. 1990;30:69-78. doi: 10.1007/978-3-7091-3345-3_7.
We studied the signal transduction system including the receptor and protein kinase C (PKC) in Alzheimer's disease (AD) brains. We used 3H-TCP as a ligand for the NMDA receptor-ion channel complex. The total concentrations of 3H-TCP binding sites were significantly reduced in AD frontal cortex. 3H-TCP binding sites spared in AD brains retained the affinity for the ligand and the reactivity to NMDA, L-glutamate, and glycine. We utilized antibodies to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC (beta II) was lower in AD particulate fractions and higher in AD cytosol fractions. Immunocytochemical studies revealed reduced numbers of anti-PKC (beta II)-immunopositive neurons. Anti-PKC (alpha) faintly stained entire plaques and surrounding glial cells. Anti-PKC (beta I) stained dystrophic plaque neurites. Anti-PKC (beta II) stained the amyloid-containing portions of plaques. These results suggest an involvement of second messenger cascades in the pathogenesis of AD in addition to neurotransmitters and their receptors.
我们研究了阿尔茨海默病（AD）大脑中的信号转导系统，包括受体和蛋白激酶C（PKC）。我们使用3H-TCP作为N-甲基-D-天冬氨酸（NMDA）受体-离子通道复合物的配体。AD额叶皮质中3H-TCP结合位点的总浓度显著降低。AD大脑中保留的3H-TCP结合位点对配体保持亲和力，并且对NMDA、L-谷氨酸和甘氨酸具有反应性。我们利用抗体来评估不同PKC亚型在AD中的参与程度。PKC（βII）的浓度在AD微粒部分中较低，而在AD胞质溶胶部分中较高。免疫细胞化学研究显示抗PKC（βII）免疫阳性神经元的数量减少。抗PKC（α）使整个斑块和周围的神经胶质细胞呈淡染色。抗PKC（βI）使营养不良性斑块神经突呈染色。抗PKC（βII）使斑块中含淀粉样蛋白的部分呈染色。这些结果表明，除了神经递质及其受体外，第二信使级联反应也参与了AD的发病机制。
