Dong Jiaxin, Li Aimin, Yamaguchi Naohiro, Sakaguchi Suehiro, Harris David A
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110, USA.
Am J Pathol. 2007 Aug;171(2):599-607. doi: 10.2353/ajpath.2007.070262. Epub 2007 Jun 14.
Doppel (Dpl) is a prion protein paralog that causes neurodegeneration when expressed ectopically in the brain. To investigate the cellular mechanism underlying this effect, we analyzed Dpl-expressing transgenic mice in which the gene for the proapoptotic protein Bax had been deleted. We found that Bax deletion does not alter either clinical symptoms or Purkinje cell degeneration in Dpl transgenic mice. In addition, we observed that degenerating Purkinje cells in these animals do not display DNA fragmentation or caspase-3 activation. Our results suggest that non-Bax-dependent pathways mediate the toxic effects of Dpl in Purkinje cells, highlighting a possible role for nonapoptotic mechanisms in the death of these neurons.
多配体蛋白聚糖（Dpl）是一种朊病毒蛋白旁系同源物，当在大脑中异位表达时会导致神经退行性变。为了研究这种效应背后的细胞机制，我们分析了表达Dpl的转基因小鼠，其中促凋亡蛋白Bax的基因已被删除。我们发现，Bax基因缺失既不改变Dpl转基因小鼠的临床症状，也不改变浦肯野细胞变性。此外，我们观察到这些动物中正在退化的浦肯野细胞没有显示出DNA片段化或半胱天冬酶-3激活。我们的结果表明，非Bax依赖性途径介导了Dpl对浦肯野细胞的毒性作用，突出了非凋亡机制在这些神经元死亡中的可能作用。
