Apoptosis In Neurodegenerative Disorders

在阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病中，神经元可能会因一种称为细胞凋亡的程序性细胞死亡而死亡。神经科学实验室细胞和分子神经科学部分的一项主要工作旨在确定在神经退行性疾病中触发细胞凋亡的原因，以及如何通过靶向细胞凋亡过程中的特定分子事件来预防神经元变性。我们发现，在阿尔茨海默病、帕金森病和亨廷顿病的实验模型中，一种名为p53的蛋白质与神经元的死亡有关。新的特异性p53抑制剂被开发出来，一些先导药物在中风和帕金森病的动物模型中显示有效。在其他研究中，我们确定了钾离子通量在脑卒中模型神经元变性发病机制中的重要作用。在中风模型中，一种叫做二氮氧化物的药物可以打开线粒体钾通道，对神经元有保护作用。我们还确定了脑源性神经营养因子（BDNF）在防止海马干细胞产生的神经元凋亡中的作用，这一发现表明有可能增加大脑替代丢失和受损神经元的能力。

In neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, neurons may die by a form of programmed cell death called apoptosis. A major effort in the Cellular and Molecular Neurosciences section of the Laboratory of Neurosciences is aimed at establishing what triggers apoptosis in neurodegenerative disorders and how neuronal degeneration might be prevented by targeting specific molecular events in the process of apoptosis. We have found that a protein called p53 is involved in the death of neurons in experimental models of Alzheimer's, Parkinson's and Huntington's diseases. Novel specific inhibitors of p53 were developed and several lead agents were shown to be effective in animal models of stroke and Parkinson's disease. In other studies we established important roles for potassium ion fluxes in the pathogenesis of neuronal degeneration in models of stroke. A drug called diazoxide that opens mitochondrial potassium channels was neuronprotective in models of stroke. We have also established roles for brain-derived neurotrophic factor (BDNF) in preventing the apoptosis of neurons produced from stem cells in the hippocampus, a finding that suggests the possibility of increasing the capacity of the brain to replace lost and damaged neurons.