Hayashi Takeshi, Shoji Mikio, Abe Koji
Department of Neurology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Curr Alzheimer Res. 2006 Sep;3(4):351-8. doi: 10.2174/156720506778249498.
There are many similarities in molecular mechanisms of neuronal cell death observed in ischemic stroke and Alzheimer's disease. From point of organelle damage, we introduced molecular events seen in ischemic stroke, and compared the findings with that observed in Alzheimer's disease. In the brain after ischemia, transmembrane potential and ion gradient are disturbed at very early stage. Several drugs are aimed to minimize this change, some of which were effective in experimental models. Calcium blocker and glutamate antagonist were also effective for Alzheimer's disease. As for mitochondrial and endoplasmic reticulum damage, both disorders share common pathological findings such as pro-apoptotic signals activation. However, there are some molecules which are neuroprotective in Alzheimer's disease but pro-apoptotic in ischemic neurons. We need to be so careful for judging the significance of a phenomenon obtained by an experiment. Lysosome, called as suicide bag, play important roles both in the brain of ischemic stroke and Alzheimer's disease. Leak of lysosomal enzymes influence, at least partially, the fate of neurons under pathological conditions in both disorders.
在缺血性中风和阿尔茨海默病中观察到的神经元细胞死亡的分子机制有许多相似之处。从细胞器损伤的角度,我们介绍了缺血性中风中出现的分子事件,并将这些发现与在阿尔茨海默病中观察到的结果进行了比较。在缺血后的大脑中,跨膜电位和离子梯度在非常早期就受到干扰。有几种药物旨在尽量减少这种变化,其中一些在实验模型中是有效的。钙阻滞剂和谷氨酸拮抗剂对阿尔茨海默病也有效。至于线粒体和内质网损伤,这两种疾病都有共同的病理发现,如促凋亡信号的激活。然而,有些分子在阿尔茨海默病中具有神经保护作用,但在缺血性神经元中却是促凋亡的。我们在判断实验获得的现象的意义时需要非常谨慎。被称为“自杀袋”的溶酶体在缺血性中风和阿尔茨海默病的大脑中都起着重要作用。溶酶体酶的泄漏至少部分地影响了这两种疾病病理条件下神经元的命运。