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  • Title: Doppel induces degeneration of cerebellar Purkinje cells independently of Bax.
    Author: Dong J, Li A, Yamaguchi N, Sakaguchi S, Harris DA.
    Journal: Am J Pathol; 2007 Aug; 171(2):599-607. PubMed ID: 17569776.
    Abstract:
    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.
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